2022/05/13 更新

写真a

ヤスハラ タカオ
安原 隆雄
YASUHARA Takao
所属
医歯薬学域 准教授
職名
准教授
外部リンク

学位

  • 医学博士 ( 2004年3月   岡山大学 )

  • 医学博士

研究キーワード

  • 感染症

  • 脳神経外傷

  • 頭蓋底外科

  • 脊椎脊髄外科

  • 中枢神経系における再生医療

研究分野

  • ライフサイエンス / 脳神経外科学

学歴

経歴

  • 岡山大学学術研究院医歯薬学域 脳神経外科   准教授

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所属学協会

委員歴

  • 日本脳神経外傷学会 代議員・広報委員  

  • 脳神経外科学会 保険診療委員・代議員  

  • 日本脳神経外科コングレス 理事・将来構想委員・教育委員  

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    団体区分:学協会

  • 日本脊髄外科学会 理事  

 

論文

  • Incidence and clinical characteristics of spinal arteriovenous shunts: hospital-based surveillance in Okayama, Japan. 国際誌

    Masafumi Hiramatsu, Ryota Ishibashi, Etsuji Suzuki, Yuko Miyazaki, Satoshi Murai, Hiroki Takai, Yuji Takasugi, Yoko Yamaoka, Kazuhiko Nishi, Yu Takahashi, Jun Haruma, Tomohito Hishikawa, Takao Yasuhara, Masaki Chin, Shunji Matsubara, Masaaki Uno, Koji Tokunaga, Kenji Sugiu, Isao Date

    Journal of neurosurgery. Spine   1 - 8   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: There have been no accurate surveillance data regarding the incidence rate of spinal arteriovenous shunts (SAVSs). Here, the authors investigate the epidemiology and clinical characteristics of SAVSs. METHODS: The authors conducted multicenter hospital-based surveillance as an inventory survey at 8 core hospitals in Okayama Prefecture between April 1, 2009, and March 31, 2019. Consecutive patients who lived in Okayama and were diagnosed with SAVSs on angiographic studies were enrolled. The clinical characteristics and the incidence rates of each form of SAVS and the differences between SAVSs at different spinal levels were analyzed. RESULTS: The authors identified a total of 45 patients with SAVSs, including 2 cases of spinal arteriovenous malformation, 5 cases of perimedullary arteriovenous fistula (AVF), 31 cases of spinal dural AVF (SDAVF), and 7 cases of spinal epidural AVF (SEAVF). The crude incidence rate was 0.234 per 100,000 person-years for all SAVSs including those at the craniocervical junction (CCJ) level. The incidence rate of SDAVF and SEAVF combined increased with advancing age in men only. In a comparative analysis between upper and lower spinal SDAVF/SEAVF, hemorrhage occurred in 7/14 cases (50%) at the CCJ/cervical level and in 0/24 cases (0%) at the thoracolumbar level (p = 0.0003). Venous congestion appeared in 1/14 cases (7%) at the CCJ/cervical level and in 23/24 cases (96%) at the thoracolumbar level (p < 0.0001). CONCLUSIONS: The authors reported detailed incidence rates of SAVSs in Japan. There were some differences in clinical characteristics of SAVSs in the upper spinal levels and those in the lower spinal levels.

    DOI: 10.3171/2021.7.SPINE21233

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  • Spinal Surgery after Bilateral Subthalamic Stimulation for Patients with Parkinson's Disease: A Retrospective Outcome Analysis of Pain and Functional Control.

    Michiari Umakoshi, Takao Yasuhara, Jun Morimoto, Satoshi Murai, Tatsuya Sasaki, Masahiro Kameda, Kyohei Kin, Yasuyuki Miyoshi, Isao Date

    Neurologia medico-chirurgica   61 ( 10 )   607 - 618   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease (PD) patients often suffer from spinal diseases requiring surgeries, although the risk of complications is high. There are few reports on outcomes after spinal surgery for PD patients with deep brain stimulation (DBS). The objective of this study was to explore the data on spinal surgery for PD patients with precedent DBS. We evaluated 24 consecutive PD patients with 28 spinal surgeries from 2007 to 2017 who received at least a 2-year follow-up. The characteristics and outcomes of PD patients after spinal surgery were compared to those of 156 non-PD patients with degenerative spinal diseases treated in 2013-2017. Then, the characteristics, outcomes, and spinal alignment of PD patients receiving DBS were analyzed in degenerative spinal/lumbar diseases. The mean age at the time of spinal surgery was 68 years. The Hoehn and Yahr score regarding PD was stage 1 for 8 patients, stage 2 for 2 patients, stage 3 for 8 patients, stage 4 for 10 patients, and stage 5 for 0 patient. The median preoperative L-DOPA equivalent daily dose was 410 mg. Thirteen patients (46%) received precedent subthalamic nucleus (STN) DBS. Lumbar lesions with pain were common, and operation and anesthesia times were long in PD patients. Pain and functional improvement of PD patients persisted for 2 years after surgery with a higher complication rate than for non-PD patients. PD patients with STN DBS maintained better lumbar lordosis for 2 years after spinal surgery. STN DBS significantly maintained spinal alignment with subsequent pain and functional amelioration 2 years after surgery. The outcomes of spinal surgery for PD patients might be favorably affected by thorough treatment for PD including DBS.

    DOI: 10.2176/nmc.oa.2021-0094

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  • Ultra-high-molecular-weight Polyethylene (UHMWPE) Wing Method for Strong Cranioplasty.

    Kazuki Kobayashi, Tadato Yukiue, Hideyuki Yoshida, Nobushige Tsuboi, Yuu Takahashi, Keigo Makino, Ryu Kimura, Ryo Mizuta, Susumu Sasada, Tomoyuki Ogawa, Noriyuki Nagayama, Takao Yasuhara, Isao Date

    Neurologia medico-chirurgica   61 ( 9 )   549 - 556   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We developed a new cranioplasty method that utilizes artificial bone made of ultra-high-molecular-weight polyethylene, with a wedge-shaped edge (UHMWPE Wing). This study shows the methods and data of case series and finite element analyses with the UHMWPE Wing. A circumferential wing was preoperatively designed for a custom-made artificial bone made of UHMWPE to achieve high fixed power and to minimize the usage of cranial implants. Here, we present 4 years of follow-up data and finite element analyses for patients treated with the UHMWPE Wing between February 2015 and February 2019. Eighteen consecutive patients underwent cranioplasty using our UHMWPE Wing design. There were no postoperative adverse events in 17 of the patients for at least 18 months. One case of hydrocephalus experienced screw loosening and graft uplift due to shunt malfunction. Placement of a ventriculo-peritoneal shunt immediately returned the artificial bone to normal position. Finite element analyses revealed that a model using the UHMWPE Wing had the highest withstand load and lowest deformation. This is the first report on the UHMWPE Wing method. This method may enable clinicians to minimize dead space and achieve high strength in cranioplasty.

    DOI: 10.2176/nmc.oa.2021-0032

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  • 脳神経外科領域における手術部位感染 招待

    安原隆雄、伊達 勲

    脳神経外科   49 ( 5 )   1093 - 1104   2021年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • [Surgical Site Infection(SSI)in Neurosurgery].

    Takao Yasuhara, Isao Date

    No shinkei geka. Neurological surgery   49 ( 5 )   1093 - 1104   2021年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Although surgical site infections(SSIs)are usually controllable, their occasional occurrence is unavoidable. SSIs in neurosurgery comprise surgical-wound infections and surgical-organ/space infections. Data from the Japan Nosocomial Infections Surveillance revealed an overall infection rate of 1.1% during the first half of 2020. Responses to two questionnaire-based surveys on SSI prevention and complications related to cranial implant/artificial bone revealed the real world situation in neurosurgery. In 2020, neurosurgical information was added to the practical guidelines concerning the proper use of prophylactic antibacterial drug for SSIs. COVID-19 hygiene control protocols may have reduced the incidence of SSIs. It may be prudent to continue this stringent hygiene control after the COVID-19 pandemic has abated. Information of medical material on SSI is presented in this article, including the Plus suture®, DuraGen®, DuraSeal®, Adherus®, ultra-high-molecular-weight polyethylene(SKULPIO®, CRANIOFIT-PE®), Bioglide® and Bactiseal® shunt systems, and olanexidine. Minimizing SSIs requires proper knowledge on infection control, taking care while performing neurosurgical procedures, and compassion for the patients. In addition, information and material must be updated over time.

    DOI: 10.11477/mf.1436204493

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  • An Evaluation of the Safety and Feasibility of Adenosine-assisted Clipping Surgery for Unruptured Cerebral Aneurysms: Study Protocol.

    Tomohito Hishikawa, Satoshi Murai, Masafumi Hiramatsu, Jun Haruma, Kazuhiko Nishi, Yuki Ebisudani, Yu Sato, Takao Yasuhara, Kenji Sugiu, Kazuyoshi Shimizu, Motomu Kobayashi, Koji Nakagawa, Aya Kimura-Ono, Katsuyuki Hotta, Hiroshi Morimatsu, Isao Date

    Neurologia medico-chirurgica   61 ( 7 )   393 - 396   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The effectiveness of adenosine-induced flow arrest in surgical clipping for the cerebral aneurysms with difficulties in temporary clip placement to the proximal main trunk has been reported. This is the first clinical trial to evaluate the safety and feasibility of adenosine-assisted clipping surgery for unruptured cerebral aneurysms (UCAs) in Japan. The inclusion criteria are as follows: patients over 20 years old, patients who agree to be enrolled in this study after providing informed consent, patients who undergo clipping surgery for UCA in our institute, and patients in whom the surgeons (T.H. or I.D.) judge that decompression of the aneurysm is effective. The primary endpoint is a modified Rankin Scale (mRS) score 30 days after surgery. We plan to enroll 10 patients in this study. The original protocol of adenosine administration was established in this trial. Herein, we present the study protocol.

    DOI: 10.2176/nmc.st.2021-0018

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  • 新時代のspinal surgery 招待 査読

    安原隆雄、伊達 勲

    脳神経外科速報   31 ( 4 )   622 - 626   2021年7月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Vagus Nerve Stimulation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson's Disease Model Rats. 国際誌

    Ittetsu Kin, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Takashi Agari, Mihoko Okazaki, Kakeru Hosomoto, Yosuke Okazaki, Satoru Yabuno, Satoshi Kawauchi, Ken Kuwahara, Jun Morimoto, Kyohei Kin, Michiari Umakoshi, Yousuke Tomita, Naoki Tajiri, Cesario V Borlongan, Isao Date

    Biomedicines   9 ( 7 )   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats. METHODS: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA). RESULTS: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy. CONCLUSIONS: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.

    DOI: 10.3390/biomedicines9070789

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  • Trends in Incidence of Intracranial and Spinal Arteriovenous Shunts: Hospital-Based Surveillance in Okayama, Japan. 国際誌

    Satoshi Murai, Masafumi Hiramatsu, Etsuji Suzuki, Ryota Ishibashi, Hiroki Takai, Yuko Miyazaki, Yuji Takasugi, Yoko Yamaoka, Kazuhiko Nishi, Yu Takahashi, Jun Haruma, Tomohito Hishikawa, Takao Yasuhara, Masaki Chin, Shunji Matsubara, Masaaki Uno, Koji Tokunaga, Kenji Sugiu, Isao Date

    Stroke   52 ( 4 )   1455 - 1459   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND PURPOSE: To date, the incidence of intracranial and spinal arteriovenous shunts has not been thoroughly investigated. We aimed to clarify recent trends in the rates of intracranial and spinal arteriovenous shunts in Japan. METHODS: We conducted multicenter hospital-based surveillance at 8 core hospitals in Okayama Prefecture between April 1, 2009 and March 31, 2019. Patients who lived in Okayama and were diagnosed with cerebral arteriovenous malformations, dural arteriovenous fistulas (DAVFs), or spinal arteriovenous shunts (SAVSs) were enrolled. The incidence and temporal trends of each disease were calculated. RESULTS: Among a total of 393 cranial and spinal arteriovenous shunts, 201 (51.1%) cases of DAVF, 155 (39.4%) cases of cerebral arteriovenous malformation, and 34 (8.7%) cases of SAVS were identified. The crude incidence rates between 2009 and 2019 were 2.040 per 100 000 person-years for all arteriovenous shunts, 0.805 for cerebral arteriovenous malformation, 1.044 for DAVF, and 0.177 for SAVS. The incidence of all types tended to increase over the decade, with a notable increase in incidence starting in 2012. Even after adjusting for population aging, the incidence of nonaggressive DAVF increased 6.0-fold while that of SAVS increased 4.4-fold from 2010 to 2018. CONCLUSIONS: In contrast to previous studies, we found that the incidence of DAVF is higher than that of cerebral arteriovenous malformation. Even after adjusting for population aging, all of the disease types tended to increase in incidence over the last decade, with an especially prominent increase in SAVSs and nonaggressive DAVFs. Various factors including population aging may affect an increase in DAVF and SAVS.

    DOI: 10.1161/STROKEAHA.120.032052

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  • Pyogenic Ventriculitis After Anterior Skull Base Surgery Treated With Endoscopic Ventricular Irrigation And Reconstruction Using a Vascularized Flap.

    Yusuke Tomita, Yosuke Shimazu, Masato Kawakami, Hiroshi Matsumoto, Kentaro Fujii, Masahiro Kameda, Takao Yasuhara, Yasuki Suruga, Tomoyuki Ota, Yoshihiro Kimata, Kazuhiko Kurozumi, Isao Date

    Acta medica Okayama   75 ( 2 )   243 - 248   2021年4月

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    記述言語:英語  

    Ventriculitis is a rare, serious complication of neurosurgery. A 59-year-old man who had undergone a craniotomy for a paranasal adenocarcinoma, developed a right frontal cystic lesion. We performed a bifrontal craniotomy to remove the lesion. The dura was repaired with non-vascularized free fascia lata in watertight fashion. Ventriculitis occurred 3 days postoperatively. Ventricular drainage, craniectomy, and endoscopic irrigation were undertaken to remove an abscess. The dura and the resection cavity were reconstructed using a vascularized anterolateral thigh adipofascial flap. His symptoms disappeared, indicating that endoscopic irrigation and reconstruction can effectively address ventriculitis even in patients in critical clinical condition.

    DOI: 10.18926/AMO/61908

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  • Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial. 国際誌

    Masahito Kawabori, Alan H Weintraub, Hideaki Imai, Laroslav Zinkevych, Peter McAllister, Gary K Steinberg, Benjamin M Frishberg, Takao Yasuhara, Jefferson W Chen, Steven C Cramer, Achal S Achrol, Neil E Schwartz, Jun Suenaga, Daniel C Lu, Ihor Semeniv, Hajime Nakamura, Douglas Kondziolka, Dai Chida, Takehiko Kaneko, Yasuaki Karasawa, Susan Paadre, Bijan Nejadnik, Damien Bates, Anthony H Stonehouse, R Mark Richardson, David O Okonkwo

    Neurology   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: To determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623). METHODS: This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1:1:1:1 ratio to 2.5 × 106, 5.0 × 106, 10 × 106 SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15). RESULTS: The primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI: 0.3-11.8); p = 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (p = 0.25). CONCLUSIONS: SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.

    DOI: 10.1212/WNL.0000000000011450

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  • Chiari奇形1型の手術におけるデュラウェーブRを用いた硬膜形成

    冨田陽介、守本 純、佐々田晋、井本良二、馬越通有、金 恭平、亀田雅博、安原隆雄、伊達 勲

    脊髄外科 SPINAL SURGERY   34 ( 3 )   317 - 319   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • FDG-PETと馬尾生検により早期診断し得た神経悪性リンパ腫症の1例 査読

    佐々木諒、太田康之、安原隆雄、伊達 勲、阿部康二

    CI研究   42 ( 2 )   127 - 130   2020年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Arteriovenous Fistula at the Craniocervical Junction Found After Cervical Laminoplasty for Ossification of the Posterior Longitudinal Ligament. 国際誌

    Susumu Sasada, Masafumi Hiramatsu, Akira Kusumegi, Haruto Fujimura, Shogo Oshikata, Yuichi Takahashi, Kenki Nishida, Takao Yasuhara, Isao Date

    Neurospine   17 ( 4 )   947 - 953   2020年12月

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    記述言語:英語  

    Ossification of the posterior longitudinal ligament (OPLL) is common in East Asia. Arteriovenous fistula at the craniocervical junction (CCJ-AVF), in contrast, is rare. As OPLL occurs most often in the cervical region, these 2 conditions can coexist in the cervical spinal canal of a single patient. We report a case of CCJ-AVF found after cervical laminoplasty (CLP) for OPLL. A 68-year-old man experienced progressive myelopathy due to cervical OPLL. Magnetic resonance imaging (MRI) revealed a high-intensity area inside the spinal cord. CLP was performed and his symptoms immediately improved. Three months after CLP, however, myelopathy recurred. MRI revealed an exacerbated and enlarged high-intensity area inside the cord from the medulla oblongata to the C4/5 level with a flow void around the cord. Left vertebral artery angiography revealed CCJ-AVF with ascending and descending draining veins. Direct surgery was performed to interrupt shunt flow into the draining veins. The patient's symptoms improved to a limited degree. In this case, increased pressure inside the spinal canal due to OPLL might have decreased the shunt flow of the CCJ-AVF. Thus, the venous congestion induced by CCJ-AVF might have been exacerbated after the pressure was removed by CLP. Magnetic resonance angiography screening could help detect concurrent CCJ-AVF and OPLL.

    DOI: 10.14245/ns.2040200.100

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  • Neurosurgical versus endovascular treatment of spinal dural arteriovenous fistulas: a multicenter study of 195 patients. 国際誌

    Keisuke Takai, Toshiki Endo, Takao Yasuhara, Toshitaka Seki, Kei Watanabe, Yuki Tanaka, Ryu Kurokawa, Hideaki Kanaya, Fumiaki Honda, Takashi Itabashi, Osamu Ishikawa, Hidetoshi Murata, Takahiro Tanaka, Yusuke Nishimura, Kaoru Eguchi, Toshihiro Takami, Yusuke Watanabe, Takeo Nishida, Masafumi Hiramatsu, Tatsuya Ohtonari, Satoshi Yamaguchi, Takafumi Mitsuhara, Seishi Matsui, Hisaaki Uchikado, Gohsuke Hattori, Hitoshi Yamahata, Makoto Taniguchi

    Journal of neurosurgery. Spine   1 - 8   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: The purpose of the present study was to compare the treatment success rates of primary neurosurgical and endovascular treatments in patients with spinal dural arteriovenous fistulas (dAVFs). METHODS: Data from 199 consecutive patients with thoracic and lumbosacral spinal dAVFs were collected from 18 centers. Angiographic and clinical findings, the rate of initial treatment failure or recurrence by procedures, risk factors for treatment failure, complications, and neurological outcomes were statistically analyzed. RESULTS: Spinal dAVFs were frequently detected in the thoracic region (81%), fed by a single feeder (86%), and shunted into an intradural vein via the dura mater. The fistulous connection between the feeder(s) and intradural vein was located at a single spinal level in 195 patients (98%) and at 2 independent levels in 4 patients (2%). Among the neurosurgical (n = 145), and endovascular (n = 50) treatment groups of single dAVFs (n = 195), the rate of initial treatment failure or recurrence was significantly higher in the index endovascular treatment group (0.68% and 36%). A multivariate analysis identified endovascular treatment as an independent risk factor with significantly higher odds of initial treatment failure or recurrence (OR 69; 95% CI 8.7-546). The rate of complications did not significantly differ between the two treatment groups (4.1% for neurosurgical vs 4.0% for endovascular treatment). With a median follow-up of 26 months, improvements of ≥ 1 point in the modified Rankin Scale (mRS) score and Aminoff-Logue gait and Aminoff-Logue micturition grades were observed in 111 (56%), 121 (61%), and 79 (40%) patients, respectively. Independent risk factors for lack of improvement in the Aminoff-Logue gait grades were multiple treatments due to initial treatment failure or recurrence (OR 3.1) and symptom duration (OR 1.02). CONCLUSIONS: Based on data obtained from the largest and most recently assessed multicenter cohort, the present study shows that primary neurosurgery is superior to endovascular treatment for the complete obliteration of spinal dAVFs by a single procedure.

    DOI: 10.3171/2020.6.SPINE20309

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  • 脳・神経疾患における再生医療の最前線 招待 査読

    安原隆雄、伊達 勲

    Precision Medicine   3 ( 11 )   980 - 983   2020年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 両側びまん性脈絡叢過形成の1例─両側びまん性脈絡叢過形成、両側脈絡叢乳頭腫に対する外科的治療に関する文献的レビュー─ 査読

    胡谷侑貴、安原隆雄、亀田雅博、福原 徹、伊達 勲

    脳神経外科ジャーナル   29 ( 10 )   726 - 734   2020年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Detection of the common origin of the radiculomedullary artery with the feeder of spinal dural arteriovenous fistula using slab maximum intensity projection image 国際誌

    Masafumi Hiramatsu, Kenji Sugiu, Takao Yasuhara, Tomohito Hishikawa, Jun Haruma, Yu Takahashi, Satoshi Murai, Kazuhiko Nishi, Yoko Yamaoka, Isao Date

    Neuroradiology   62 ( 10 )   1285 - 1292   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    PURPOSE: Endovascular therapy to the spinal dural arteriovenous fistula (SDAVF) with a common origin of the radiculomedullary artery and the feeder of the shunt has the risk of spinal cord infarction. This study aimed to retrospectively assess the detection rate of normal spinal arteries from the feeder of SDAVF. METHODS: We retrospectively collected the angiographic and clinical data of SDAVFs. This study included 19 patients with 20 SDAVF lesions admitted to our department between January 2007 and December 2018. We assessed the detection rate of normal radiculomedullary artery branched from the feeder of SDAVF between the period using the image intensifier (II) and flat panel detector (FPD) and evaluated the treatment results. RESULTS: The detection rates of the radiculomedullary artery branched from the feeder of SDAVF were 10% (1/10 lesions) during the II period and 30% (3/10 lesions) during the FPD period. During the FPD period, all normal radiculomedullary arteries branched from the feeder were only detected on slab maximum intensity projection (MIP) images of rotational angiography, and we could not detect them in 2D or 3D digital subtraction angiography. All lesions that had a common origin of a normal radiculomedullary artery and the feeder were completely obliterated without complications. There was no recurrence during the follow-up period. CONCLUSIONS: The flat panel detector and slab MIP images seem to show the common origin of the normal radiculomedullary arteries from the feeder more accurately. With detailed analyses, SDAVF can be safety treated.

    DOI: 10.1007/s00234-020-02466-0

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    その他リンク: http://link.springer.com/article/10.1007/s00234-020-02466-0/fulltext.html

  • Detection of the common origin of the radiculomedullary artery with the feeder of spinal dural arteriovenous fistula using slab maximum intensity projection image

    Masafumi Hiramatsu, Kenji Sugiu, Takao Yasuhara, Tomohito Hishikawa, Jun Haruma, Yu Takahashi, Satoshi Murai, Kazuhiko Nishi, Yoko Yamaoka, Isao Date

    NEURORADIOLOGY   62 ( 10 )   1285 - 1292   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Purpose Endovascular therapy to the spinal dural arteriovenous fistula (SDAVF) with a common origin of the radiculomedullary artery and the feeder of the shunt has the risk of spinal cord infarction. This study aimed to retrospectively assess the detection rate of normal spinal arteries from the feeder of SDAVF. Methods We retrospectively collected the angiographic and clinical data of SDAVFs. This study included 19 patients with 20 SDAVF lesions admitted to our department between January 2007 and December 2018. We assessed the detection rate of normal radiculomedullary artery branched from the feeder of SDAVF between the period using the image intensifier (II) and flat panel detector (FPD) and evaluated the treatment results. Results The detection rates of the radiculomedullary artery branched from the feeder of SDAVF were 10% (1/10 lesions) during the II period and 30% (3/10 lesions) during the FPD period. During the FPD period, all normal radiculomedullary arteries branched from the feeder were only detected on slab maximum intensity projection (MIP) images of rotational angiography, and we could not detect them in 2D or 3D digital subtraction angiography. All lesions that had a common origin of a normal radiculomedullary artery and the feeder were completely obliterated without complications. There was no recurrence during the follow-up period. Conclusions The flat panel detector and slab MIP images seem to show the common origin of the normal radiculomedullary arteries from the feeder more accurately. With detailed analyses, SDAVF can be safety treated.

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  • Microsurgical versus endovascular treatment of spinal epidural arteriovenous fistulas with intradural venous drainage: a multicenter study of 81 patients 国際誌

    Keisuke Takai, Toshiki Endo, Takao Yasuhara, Toshitaka Seki, Kei Watanabe, Yuki Tanaka, Ryu Kurokawa, Hideaki Kanaya, Fumiaki Honda, Takashi Itabashi, Osamu Ishikawa, Hidetoshi Murata, Yusuke Nishimura, Kaoru Eguchi, Toshihiro Takami, Yusuke Watanabe, Takeo Nishida, Masafumi Hiramatsu, Tatsuya Ohtonari, Satoshi Yamaguchi, Takafumi Mitsuhara, Seishi Matsui, Hisaaki Uchikado, Gohsuke Hattori, Nobutaka Horie, Hitoshi Yamahata, Makoto Taniguchi

    JOURNAL OF NEUROSURGERY-SPINE   33 ( 3 )   381 - 391   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC NEUROLOGICAL SURGEONS  

    OBJECTIVE Spinal arteriovenous shunts are rare vascular lesions and are classified into 4 types (types I-IV). Due to rapid advances in neuroimaging, spinal epidural AVFs (edAVFs), which are similar to type I spinal dural AVFs (dAVFs), have recently been increasingly reported. These 2 entities have several important differences that influence the treatment strategy selected. The purposes of the present study were to compare angiographic and clinical differences between edAVFs and dAVFs and to provide treatment strategies for edAVFs based on a multicenter cohort.METHODS A total of 280 consecutive patients with thoracic and lumbosacral spinal dural arteriovenous fistulas (dAVFs) and edAVFs with intradural venous drainage were collected from 19 centers. After angiographic and clinical comparisons, the treatment failure rate by procedure, risk factors for treatment failure, and neurological outcomes were statistically analyzed in edAVF cases.RESULTS Final diagnoses after an angiographic review included 199 dAVFs and 81 edAVFs. At individual centers, 29 patients (36%) with edAVFs were misdiagnosed with dAVFs. Spinal edAVFs were commonly fed by multiple feeding arteries (54%) shunted into a single or multiple intradural vein(s) (91% and 9%) through a dilated epidural venous plexus. Preoperative modified Rankin Scale (mRS) and Aminoff Logue gait and micturition grades were worse in patients with edAVFs than in those with dAVFs. Among the microsurgical (n = 42), endovascular (n = 36), and combined (n = 3) treat- ment groups of edAVFs, the treatment failure rate was significantly higher in the index endovascular treatment group (7.5%, 31%, and 0%, respectively). Endovascular treatment was found to be associated with significantly higher odds of initial treatment failure (OR 5.72, 95% CI 1.45-22.6). In edAVFs, the independent risk factor for treatment failure after microsurgery was the number of intradural draining veins (OR 17.9, 95% C11.56-207), while that for treatment failure after the endovascular treatment was the number of feeders (OR 4.11, 95% CI 1.23-13.8). Postoperatively, mRS score and Aminoff-Logue gait and micturition grades significantly improved in edAVFs with a median follow-up of 31 months.CONCLUSIONS Spinal epidural AVFs with intradural venous drainage are a distinct entity and may be classified as type V spinal vascular malformations. Based on the largest multicenter cohort, this study showed that primary microsurgery was superior to endovascular treatment for initial treatment success in patients with spinal edAVFs.

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  • Japanese National Questionnaire Survey in 2018 on Complications Related to Cranial Implants in Neurosurgery.

    Takao Yasuhara, Satoshi Murai, Nobuhiro Mikuni, Susumu Miyamoto, Isao Date

    Neurologia medico-chirurgica   60 ( 7 )   337 - 350   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cranial implants are commonly used throughout the world, yet the data on complications remain partly clarified. The aim of this study was to gather real data in 2018 on complications related to cranial implants in neurosurgery. The survey population consisted of 1103 institutes supplying neurosurgical treatment. The survey consisted of two-stage questionnaire. First the incidence of complications was investigated, then the secondary questionnaire was e-mailed to the respondents about the detailed of the complications. As the result, the annual incidence of complications related to cranial implants was 0.558% in Japan. Titanium plate and mesh were used predominantly in craniotomy and cranioplasty, respectively. The second survey collected data on 449 cases with complications (infection: 63%, implant exposure: 46%, multiple answer). Postoperative infection was associated with male sex, brain tumor, short interval between surgery and complication, usage of ceramics, hydroxyapatite, resin, and artificial dura, hyponutrition, multiple surgeries, dirty wound, and sinusitis as patient factors, and CSF leakage, ruptured sutures, and sinus maltreatment as surgery factors. Meanwhile, long hospital stay was associated with age, male sex, mRS 3-5 before complication, short interval between initial surgery and complication, large craniotomy, long operative time, usage of ceramics and artificial dura, multiple surgeries and dirty wound as patient factors, ruptured suture as a surgical factor, and bacterial infection, especially MRSA infection, as the complication and treatment consisting of removal as complication factors. In conclusion, this is the first Japanese national survey on complications related to cranial implants in neurosurgery. It is important to recall that complications may arise years after surgery and to be aware of the risk factors associated with complications.

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  • Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats. 国際誌

    Naoya Kidani, Tomohito Hishikawa, Masafumi Hiramatsu, Shingo Nishihiro, Kyohei Kin, Yu Takahashi, Satoshi Murai, Kenji Sugiu, Takao Yasuhara, Ikuko Miyazaki, Masato Asanuma, Isao Date

    International journal of molecular sciences   21 ( 11 )   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for "oxidative phosphorylation" was significantly upregulated while fourteen other gene sets including "apoptosis", "hypoxia" and "reactive oxygen species" showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

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  • Cell therapy for central nervous system disorders: Current obstacles to progress. 査読 国際誌

    Takao Yasuhara, Satoshi Kawauchi, Kyohei Kin, Jun Morimoto, Masahiro Kameda, Tatsuya Sasaki, Brooke Bonsack, Chase Kingsbury, Naoki Tajiri, Cesario V Borlongan, Isao Date

    CNS neuroscience & therapeutics   26 ( 6 )   595 - 602   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cell therapy for disorders of the central nervous system has progressed to a new level of clinical application. Various clinical studies are underway for Parkinson's disease, stroke, traumatic brain injury, and various other neurological diseases. Recent biotechnological developments in cell therapy have taken advantage of the technology of induced pluripotent stem (iPS) cells. The advent of iPS cells has provided a robust stem cell donor source for neurorestoration via transplantation. Additionally, iPS cells have served as a platform for the discovery of therapeutics drugs, allowing breakthroughs in our understanding of the pathology and treatment of neurological diseases. Despite these recent advances in iPS, adult tissue-derived mesenchymal stem cells remain the widely used donor for cell transplantation. Mesenchymal stem cells are easily isolated and amplified toward the cells' unique trophic factor-secretion property. In this review article, the milestone achievements of cell therapy for central nervous system disorders, with equal consideration on the present translational obstacles for clinic application, are described.

    DOI: 10.1111/cns.13247

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  • Correction to: High‑Mobility Group Box‑1‑Induced Angiogenesis After Indirect Bypass Surgery in a Chronic Cerebral Hypoperfusion Model. 国際誌

    Shingo Nishihiro, Tomohito Hishikawa, Masafumi Hiramatsu, Naoya Kidani, Yu Takahashi, Satoshi Murai, Kenji Sugiu, Yusuke Higaki, Takao Yasuhara, Cesario V Borlongan, Isao Date

    Neuromolecular medicine   22 ( 2 )   332 - 333   2020年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The original version of this article unfortunately contained a mistake. Figure 5a, b were incorrect. The correct figures are given below.

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  • 神経根ブロック後、腰椎圧迫骨折偽関節部が形成に関与した脊柱管内嚢胞性腫瘤の1例 査読

    三好康之、安原隆雄、眞鍋博明、服部靖彦

    脊髄外科 SPINAL SURGERY   34 ( 1 )   66 - 72   2020年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 術前Short Form-36は脊椎変性疾患術後せん妄発症を予測する 査読

    金 恭平、安原隆雄、守本 純、馬越通有、冨田陽介、伊達 勲

    脊髄外科 SPINAL SURGERY   34 ( 1 )   95 - 97   2020年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 脊髄電気刺激は神経保護効果を有するか─パーキンソン病の再生医療─ 査読

    安原隆雄、守本 純、金 恭平、佐々木達也、伊達 勲

    脊髄外科 SPINAL SURGERY   34 ( 1 )   90 - 91   2020年4月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Study protocol of a Phase I/IIa clinical trial of Ad-SGE-REIC for treatment of recurrent malignant glioma. 国際誌

    Kazuhiko Kurozumi, Kentaro Fujii, Yosuke Shimazu, Yusuke Tomita, Tatsuya Sasaki, Takao Yasuhara, Tomohito Hishikawa, Masahiro Kameda, Hiromi Kumon, Isao Date

    Future oncology (London, England)   16 ( 6 )   151 - 159   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Malignant glioma is one of the most common brain cancers in humans, which is very devastating. The expression of reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is decreased in various human cancers. Lately, we have developed a novel second-generation adenoviral vector that expresses REIC/Dkk-3 (Ad-SGE-REIC) and revealed its antiglioma efficacy. The present investigator-initiated clinical trial is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed at Okayama University Hospital, Okayama, Japan. The primary end points are dose-limiting toxicities and the incidence of adverse events. The secondary end points are the objective response rate and immunological assessment. Use of Ad-SGE-REIC will help to improve the prognosis of patients with malignant brain tumors.

    DOI: 10.2217/fon-2019-0743

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  • Precise MEP monitoring with a reduced interval is safe and useful for detecting permissive duration for temporary clipping 国際誌

    Masahiro Kameda, Tomohito Hishikawa, Masafumi Hiramatsu, Takao Yasuhara, Kazuhiko Kurozumi, Isao Date

    SCIENTIFIC REPORTS   10 ( 1 )   3507 - 3507   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Although temporary clipping of the parent artery is an indispensable technique in clipping surgery for intracranial aneurysms, the permissive duration of temporary clipping is still not well known. The aim of this study is to confirm the safety of precise motor evoked potential (MEP) monitoring and to estimate the permissive duration of temporary clipping for middle cerebral artery (MCA) aneurysm based on precise MEP monitoring results. Under precise MEP monitoring via direct cortical stimulation every 30 seconds to 1 minute, surgeons released a temporary clip and waited for MEP amplitude to recover following severe (>50%) reduction of MEP amplitude during temporary clipping. Precise MEP monitoring was safely performed. Twenty-eight instances of temporary clipping were performed in 42 MCA aneurysm clipping surgeries. Because precise MEP monitoring could be used to determine when to release a temporary clip even with a severe reduction in MEP amplitude due to lengthy temporary clipping, no patients experienced permanent postoperative hemiparesis. Based on logistic regression analysis, if a temporary clip is applied for 312 seconds or more, there is a higher probability of a severe reduction in MEP amplitude. We should therefore release temporary clips after 5 minutes in order to avoid permanent postoperative hemiparesis.

    DOI: 10.1038/s41598-020-60377-9

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  • Neurobiology Research in Parkinson's Disease. 国際誌

    Takao Yasuhara

    International journal of molecular sciences   21 ( 3 )   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In recent years, therapeutic strategies [...].

    DOI: 10.3390/ijms21030793

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  • Long-Term Continuous Cervical Spinal Cord Stimulation Exerts Neuroprotective Effects in Experimental Parkinson's Disease. 国際誌

    Ken Kuwahara, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Yosuke Okazaki, Kakeru Hosomoto, Ittetsu Kin, Mihoko Okazaki, Satoru Yabuno, Satoshi Kawauchi, Yousuke Tomita, Michiari Umakoshi, Kyohei Kin, Jun Morimoto, Jea-Young Lee, Naoki Tajiri, Cesar V Borlongan, Isao Date

    Frontiers in aging neuroscience   12   164 - 164   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Spinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson's disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients. Objective: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats. Methods: We developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis. Results: The 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group. Conclusions: This study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms.

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  • Encapsulation of Mesenchymal Stem Cells: Dissecting the Underlying Mechanism of Mesenchymal Stem Cell Transplantation Therapy. 国際誌

    Kyohei Kin, Takao Yasuhara, Isao Date

    Neuroscience insights   15   2633105520959064 - 2633105520959064   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mesenchymal stem cells (MSCs) are widely considered good candidates for cell transplantation therapy. Various central nervous system disorders have been suggested as suitable targets for MSC transplantation therapy. In this context, a great deal of basic and clinical research has been conducted to explore its clinical uses. Although depression is one of the most common diseases in the world, the response rate to the currently available treatment is insufficient and new treatments are much needed. Despite the fact that MSC transplantation therapy has the potential to elicit an antidepressant effect, few studies have been conducted on this topic to date and the underlying mechanism remains poorly understood. To address the development of a new treatment for depression, we evaluated the effect of MSCs using the encapsulation technique and Wistar-Kyoto rats. Encapsulation enables dissection of the complicated underlying mechanism of MSC transplantation therapy. Wistar-Kyoto rats that exhibit treatment-resistant depressive-like behaviors allow us to compare the effect of MSCs with that of conventional antidepressant treatment. In this commentary, we briefly summarize our recent published results and discuss future research prospects.

    DOI: 10.1177/2633105520959064

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  • パーキンソン病モデルラットに対する持続脊髄電気刺激療法の有用性 査読

    桑原 研、佐々木達也、岡崎洋介、細本 翔、金 一徹、藪野 諭、河内 哲、冨田陽介、馬越通有、亀田雅博、安原隆雄、伊達 勲

    機能的脳神経外科   58   45 - 51   2019年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • High-Mobility Group Box-1-Induced Angiogenesis After Indirect Bypass Surgery in a Chronic Cerebral Hypoperfusion Model 国際誌

    Shingo Nishihiro, Tomohito Hishikawa, Masafumi Hiramatsu, Naoya Kidani, Yu Takahashi, Satoshi Murai, Kenji Sugiu, Yusuke Higaki, Takao Yasuhara, Cesario Borlongan, Isao Date

    NEUROMOLECULAR MEDICINE   21 ( 4 )   391 - 400   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HUMANA PRESS INC  

    High-mobility group box-1 (HMGB1) is a nuclear protein that promotes inflammation during the acute phase post-stroke, and enhances angiogenesis during the delayed phase. Here, we evaluated whether indirect revascularization surgery with HMGB1 accelerates brain angiogenesis in a chronic cerebral hypoperfusion model. Seven days after hypoperfusion induction, encephalo-myo-synangiosis (EMS) was performed with or without HMGB1 treatment into the temporal muscle. We detected significant increments in cortical vasculature (p<0.01), vascular endothelial growth factor (VEGF) expression in the temporal muscle (p<0.05), and ratio of radiation intensity on the operated side compared with the non-operated side after EMS in the HMGB1-treated group than in the control group (p<0.01). Altogether, HMGB1 with EMS in a chronic hypoperfusion model promoted brain angiogenesis in a VEGF-dependent manner, resulting in cerebral blood flow improvement. This treatment may be an effective therapy for patients with moyamoya disease.

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  • Animal Models for Parkinson's Disease Research: Trends in the 2000s. 国際誌

    Kyohei Kin, Takao Yasuhara, Masahiro Kameda, Isao Date

    International journal of molecular sciences   20 ( 21 )   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease (PD) is a chronic and progressive movement disorder and the second most common neurodegenerative disease. Although many studies have been conducted, there is an unmet clinical need to develop new treatments because, currently, only symptomatic therapies are available. To achieve this goal, clarification of the pathology is required. Attempts have been made to emulate human PD and various animal models have been developed over the decades. Neurotoxin models have been commonly used for PD research. Recently, advances in transgenic technology have enabled the development of genetic models that help to identify new approaches in PD research. However, PD animal model trends have not been investigated. Revealing the trends for PD research will be valuable for increasing our understanding of the positive and negative aspects of each model. In this article, we clarified the trends for animal models that were used to research PD in the 2000s, and we discussed each model based on these trends.

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  • Identification of Somatotopic Organization and Optimal Stimulation Site Within the Subthalamic Nucleus for Parkinson's Disease. 国際誌

    Tatsuya Sasaki, Ken Kuwahara, Ittetsu Kin, Mihoko Okazaki, Susumu Sasada, Aiko Shinko, Masahiro Kameda, Takao Yasuhara, Takashi Agari, Isao Date

    Operative neurosurgery (Hagerstown, Md.)   17 ( 3 )   239 - 246   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Details of the somatotopy within the subthalamic nucleus (STN) are still poorly understood; however, the STN is a common target of deep brain stimulation (DBS) for Parkinson disease. OBJECTIVE: To examine somatotopic organization within the STN and identify optimal stimulation sites from 77 surgical cases with microelectrode recording. METHODS: STN-DBS was performed for 77 patients with Parkinson disease between 2010 and 2014. We performed passive movements of each joint and captured single neuronal activities to identify movement-related cells (MRCs). The sites of MRCs and active contacts were determined by measuring their distances from the first contact of DBS electrode. Their positional correlations were directly and indirectly analyzed. RESULTS: The number of obtained MRCs was 264, of which 151 responded to multiple joints. The average x-, y-, and z-coordinates of the cells of the upper and lower limbs from the midcommisural point were 13.1 ± 1.1 and 12.7 ± 1.2, 0.22 ± 1.3 and -0.45 ± 1.5, and -2.5 ± 1.1 and -3.0 ± 1.4 mm, respectively. Most MRCs were distributed in the upper third of the STN, in its superior, lateral, and posterior regions, along the DBS electrode routes. Active contacts were observed to lie slightly inferior, medial, and posterior to the average MRC position. CONCLUSION: Somatotopic organization of the STN was easier to observe in the present study than in previous studies. Optimal stimulation sites were located inferior, medial, and posterior to the average MRC location. The sites may correspond to associative or motor parts through which fibers from the supplementary motor area pass.

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  • Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats. 国際誌

    Kyohei Kin, Takao Yasuhara, Satoshi Kawauchi, Masahiro Kameda, Kakeru Hosomoto, Yousuke Tomita, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoya Kidani, Jun Morimoto, Tatsuya Sasaki, Isao Date

    Brain research   1717   52 - 59   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Wistar Kyoto (WKY) rats are a useful animal model of treatment-resistant depression. Lithium is effective for treating recurrent mood disorders or treatment-resistant depression, and lithium augmentation treatment is also useful for treatment-resistant depression. However, the treatment effect of lithium on the depressive behavior of WKY rats remains poorly understood, and whether lithium augments the treatment effect of antidepressants in WKY rats is also unknown. In this study, we evaluated the treatment effect of lithium in WKY rats. We also sought to determine if lithium treatment augments the treatment effect of fluoxetine. Lithium was administered for 15 consecutive days and fluoxetine was administered 23.5, 5, and 1 h before the forced swim test (FST) day 2, based on previous studies. Lithium treatment counteracted depressive behavior in the FST and increased hippocampal neurogenesis. Additionally, co-administration of lithium and fluoxetine augmented the treatment effect observed in the FST and in hippocampal neurogenesis in WKY rats, although fluoxetine monotherapy showed no treatment effect. Lithium prevented an increase in body weight, similar to its effect in human patients. These results are consistent with those of lithium augmentation treatment for human patients with treatment-resistant depression. They suggest that WKY rats are a promising animal model for treatment-resistant depression. However, lithium treatment has various side effects. A new treatment with the same anti-depressive effect as fluoxetine + lithium treatment and fewer side effects compared with lithium would be desirable for patients with treatment-resistant depression.

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  • 小児脳腫瘍の手術:手術手技と合併症回避 小児脳腫瘍に対する鏡視下手術

    黒住 和彦, 亀田 雅博, 藤井 謙太郎, 冨田 祐介, 安原 隆雄, 伊達 勲

    小児の脳神経   44 ( 2 )   137 - 137   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • Delayed postoperative hyponatremia after endoscopic transsphenoidal surgery for pituitary adenoma. 国際誌

    Yusuke Tomita, Kazuhiko Kurozumi, Kenichi Inagaki, Masahiro Kameda, Joji Ishida, Takao Yasuhara, Tomotsugu Ichikawa, Tomoko Sonoda, Fumio Otsuka, Isao Date

    Acta neurochirurgica   161 ( 4 )   707 - 715   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Hyponatremia generally occurs after transsphenoidal surgery (TSS) in a delayed fashion. Most patients with delayed postoperative hyponatremia (DPH) are asymptomatic or only express non-specific symptoms; consequently, DPH is associated with prolonged hospitalization. No consensus has been reached on which patients are at greatest risk of developing DPH. We reviewed patients with DPH and evaluated predictive factors for DPH. METHODS: We retrospectively analyzed 107 consecutive patients who underwent endoscopic TSS for pituitary adenoma (January 2010-December 2016). Patients with DPH (hyponatremia group) and without DPH (normonatremia group) were compared according to their nadir sodium levels on postoperative days 3 to 10. We documented the patients' demographics, clinical features, and postoperative physiological characteristics. RESULTS: Twenty-five (23.4%) patients developed DPH after endoscopic TSS. The patients' mean age was 54 ± 17 years, and 63.6% of the patients were female. The overall prevalence of DPH was 23.4%. The non-parametric χ2 test and the Mann-Whitney U test revealed statistically significant differences in age, use of antihypertensive drugs, nonfunctioning pituitary adenoma, and higher yet normal preoperative thyroid-stimulating hormone level between the hyponatremia and normonatremia groups (P < 0.05). Logistic regression analysis revealed that only older age was a useful independent predictive factor for DPH (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; P = 0.01). The serum sodium levels on postoperative day 2 were significantly lower in the hyponatremia than normonatremia group (P < 0.01) and were negatively correlated with age (r = - 0.25, P < 0.05). The cut-off age for predicting DPH was 55 years. The hospital stay was significantly longer in the hyponatremia than normonatremia group (P < 0.01). CONCLUSIONS: Age of more than 55 years was an independent predictive factor for DPH even after adjusting for potential confounders. Older age was negatively correlated with the serum sodium level on postoperative day 2. Preventing early decreases in the sodium level could reduce the risk of DPH. TRIAL REGISTRATION: 1707-027.

    DOI: 10.1007/s00701-019-03818-3

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  • 中枢神経系疾患における神経新生とうつ病様症状─細胞移植、電気刺激、リハビリテーションによる治療─ 招待

    金 恭平、安原隆雄、伊達 勲

    Medical Science Digest (MSD)   45 ( 3 )   132 - 135   2019年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Comparison between spinal dural arteriovenous fistula and spinal epidural arteriovenous fistula 査読 国際誌

    Hiramatsu M, Sugiu K, Yasuhara T, Hishikawa T, Nishihiro S, Kidani N, Takahashi Y, Murai S, Date I

    Journal of Neuroendovascular Therapy   13 ( 3 )   114 - 119   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • SF-36 scores predict postoperative delirium after surgery for cervical spondylotic myelopathy. 国際誌

    Kyohei Kin, Takao Yasuhara, Yousuke Tomita, Michiari Umakoshi, Jun Morimoto, Isao Date

    Journal of neurosurgery. Spine   1 - 6   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVECervical spondylotic myelopathy (CSM) is one of the most common causes of spinal cord dysfunction. Surgery for CSM is generally effective, but postoperative delirium is a potential complication. Although there have been some studies that investigated postoperative delirium after spine surgery, no useful tool for identifying high-risk patients has been established, and it is unknown if 36-Item Short Form Health Survey (SF-36) scores can predict postoperative delirium. The objective of this study was to evaluate the correlation between preoperative SF-36 scores and postoperative delirium after surgery for CSM.METHODSSixty-seven patients who underwent surgery for CSM at the authors' institution were enrolled in this study. Medical records of these patients were retrospectively reviewed. Patient background, preoperative laboratory data, preoperative SF-36 scores, the preoperative Japanese Orthopaedic Association (JOA) score for the evaluation of cervical myelopathy, and perioperative factors were selected as potential risk factors for postoperative delirium. These factors were evaluated using univariable and multivariable logistic regression analysis.RESULTSTen patients were diagnosed with postoperative delirium. Univariable analysis revealed that the physical functioning score (p = 0.01), general health perception score (p < 0.01), and vitality score (p < 0.01) of the SF-36 were significantly lower in patients with postoperative delirium than in those without. The total number of medications was significantly higher in the delirium group compared with the no-delirium group (p = 0.02). In contrast, there were no significant differences between the delirium group and the no-delirium group in cervical JOA scores (p = 0.20). Multivariable analysis revealed that a low general health perception score was an independent risk factor for postoperative delirium (p = 0.02; odds ratio 0.810, 95% confidence interval 0.684-0.960).CONCLUSIONSSome of the SF-36 scores were significantly lower in patients with postoperative delirium than in those without. In particular, the general health perception score was independently correlated with postoperative delirium. SF-36 scores could help identify patients at high risk for postoperative delirium and aid in the development of prevention strategies.

    DOI: 10.3171/2018.11.SPINE181031

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  • Anti-High Mobility Group Box 1 Antibody Therapy May Prevent Cognitive Dysfunction After Traumatic Brain Injury. 国際誌

    Yu Okuma, Hidenori Wake, Kiyoshi Teshigawara, Yu Takahashi, Tomohito Hishikawa, Takao Yasuhara, Shuji Mori, Hideo K Takahashi, Isao Date, Masahiro Nishibori

    World neurosurgery   122   e864-e871   2019年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. METHODS: TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. RESULTS: Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. CONCLUSIONS: The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

    DOI: 10.1016/j.wneu.2018.10.164

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  • Characteristics and prognostic factors of Parkinson's disease patients with abnormal postures subjected to subthalamic nucleus deep brain stimulation. 国際誌

    Mihoko Okazaki, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Takashi Agari, Ittetsu Kin, Ken Kuwahara, Jun Morimoto, Kyohei Kin, Michiari Umakoshi, Yousuke Tomita, Cesario V Borlongan, Isao Date

    Parkinsonism & related disorders   57   44 - 49   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: In Parkinson's disease (PD), abnormal postures are often accompanied, which interfere with rehabilitation and subsequent functional recovery. This study investigated the relationship between clinical characteristics and improvement in abnormal postures of PD patients who received subthalamic nucleus deep brain stimulation (STN-DBS). METHODS: Seventy-four PD patients were included in this study. Clinical data were analyzed using the patients' functional status at pre- and post-STN-DBS, including anteflexion vs. non-anteflexion, scoliosis vs. non-scoliosis, improved anteflexion vs. non-improved anteflexion, and improved scoliosis vs. non-improved scoliosis. RESULTS: In patients with anteflexion, UPDRS III motor score at off medication was worse than that of patients with non-anteflexion. Patients with scoliosis presented with more comorbid spinal deformity and longer disease duration than those without scoliosis. Cobb angle of patients with asymmetrical psoas major and erector spinal muscles was more than that of patients without the asymmetry. Patients with improved anteflexion after STN-DBS had thicker abdominal oblique muscle and transverse abdominal muscle than those of patients without improved anteflexion. Patients with improved scoliosis were significantly younger at PD onset than those without improvement. CONCLUSIONS: There were only a few prognostic factors recognized in patients with improved postures. The thick abdominal muscle for anteflexion and younger PD onset for scoliosis were significant factors for improvement by STN-DBS. Rehabilitation designed to maintain muscle for correct postures may contribute to the amelioration of abnormal postures by STN-DBS, although multicenter trials are needed.

    DOI: 10.1016/j.parkreldis.2018.07.014

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  • Cervical compressive myelopathy caused by malfunction of a programmable cerebrospinal fluid shunt valve

    Kota Sato, Toru Yamashita, Keichiro Tsunoda, Mami Takemoto, Nozomi Hishikawa, Jinwei Shang, Yasuyuki Ohta, Ken Kuwahara, Takao Yasuhara, Isao Date, Koji Abe

    INTERDISCIPLINARY NEUROSURGERY-ADVANCED TECHNIQUES AND CASE MANAGEMENT   14   183 - 185   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    The primary treatment for hydrocephalus is ventricular shunt placement, and a programmable valve is widely used for ventriculoperitoneal (VP) shunt surgery to reduce over/under drainage of cerebrospinal fluid (CSF). Here, we report a rare case of a patient who developed successive VP shunt malfunction causing spastic muscle weakness in extremities associated cervical epidural venous distension and compressive myelopathy due to over-drainage of CSF through a defective VP shunt valve a decade after the initial shunt was placed. One should be aware and cognizant of this complication and carefully follow the symptoms and potentially utilize brain MRI with and without contrast to look at over drainage stigmata to avoid the development of neurological complications.

    DOI: 10.1016/j.inat.2018.08.009

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  • 神経保護と再生に対するリハビリテーションの効果 招待

    安原隆雄、伊達 勲

    総合リハビリテーション   46 ( 11 )   1029 - 1032   2018年11月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 脳神経外科脊椎脊髄外来における漢方薬の使用 査読

    安原隆雄、伊達 勲

    脳神経外科と漢方   4   54 - 56   2018年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 高度救命救急センター発足後5年間で、救急搬送され開頭血腫除去術を受けた頭部外傷症例─予後良好群の特徴─ 査読

    安原隆雄、菱川朋人、亀田雅博、黒住和彦、伊達 勲

    神経外傷   41 ( 1 )   33 - 35   2018年9月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats. 査読 国際誌

    Kyohei Kin, Takao Yasuhara, Masahiro Kameda, Yousuke Tomita, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoya Kidani, Jun Morimoto, Mihoko Okazaki, Tatsuya Sasaki, Naoki Tajiri, Cesario V Borlongan, Isao Date

    Molecular psychiatry   25 ( 6 )   1202 - 1214   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Despite the advances in pharmacological therapies, only the half of depressed patients respond to currently available treatment. Thus, the need for further investigation and development of effective therapies, especially those designed for treatment-resistant depression, has been sorely needed. Although antidepressant effects of mesenchymal stem cells (MSCs) have been reported, the potential benefit of this cell therapy on treatment-resistant depression is unknown. Cell encapsulation may enhance the survival rate of grafted cells, but the therapeutic effects and mechanisms mediating encapsulation of MSCs remain unexplored. Here, we showed that encapsulation enhanced the antidepressant effects of MSCs by attenuating depressive-like behavior of Wistar Kyoto (WKY) rats, which are considered as a promising animal model of treatment-resistant depression. The implantation of encapsulated MSCs (eMSCs) into the lateral ventricle counteracted depressive-like behavior and enhanced the endogenous neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampus, whereas the implantation of MSCs without encapsulation or the implantation of eMSCs into the striatum did not show such ameliorative effects. eMSCs displayed robust and stable secretion of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2, and ciliary neurotrophic factor (CNTF), and the implantation of eMSCs into the lateral ventricle activated relevant pathways associated with these growth factors. Additionally, eMSCs upregulated intrinsic expression of VEGF and CNTF and their receptors. This study suggests that the implantation of eMSCs into the lateral ventricle exerted antidepressant effects likely acting via neurogenic pathways, supporting their utility for depression treatment.

    DOI: 10.1038/s41380-018-0208-0

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  • Efficacy of Dural Sealant System for Preventing Brain Shift and Improving Accuracy in Deep Brain Stimulation Surgery.

    Tatsuya Sasaki, Takashi Agari, Ken Kuwahara, Ittetsu Kin, Mihoko Okazaki, Susumu Sasada, Aiko Shinko, Masahiro Kameda, Takao Yasuhara, Isao Date

    Neurologia medico-chirurgica   58 ( 5 )   199 - 205   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The success of deep brain stimulation (DBS) depends heavily on surgical accuracy, and brain shift is recognized as a significant factor influencing accuracy. We investigated the factors associated with surgical accuracy and showed the effectiveness of a dural sealant system for preventing brain shift in 32 consecutive cases receiving DBS. Thirty-two patients receiving DBS between March 2014 and May 2015 were included in this study. We employed conventional burr hole techniques for the first 18 cases (Group I) and a dural sealant system (DuraSeal) for the subsequent 14 cases (Group II). We measured gaps between the actual positions of electrodes and the predetermined target positions. We then retrospectively evaluated the factors involved in surgical accuracy. The average gap between an electrode's actual and target positions was 1.55 ± 0.83 mm in all cases. Postoperative subdural air volume e, the only factor associated with surgical accuracy (r = 0.536, P < 0.0001), was significantly smaller in Group II (Group I: 43.9 ± 27.7, Group II: 12.1 ± 12.5 ml, P = 0.0006). The average electrode position gap was also significantly smaller in Group II (Group I: 1.77 ± 0.91, Group II: 1.27 ± 0.59 mm, P = 0.035). Use of a dural sealant system could significantly reduce intracranial air volume, which should improve surgical accuracy.

    DOI: 10.2176/nmc.oa.2017-0242

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  • The Factors Affecting the Difficulty of Percutaneous Cylindrical Electrode Placement for Spinal Cord Stimulation. 国際誌

    Kyohei Kin, Takashi Agari, Takao Yasuhara, Yousuke Tomita, Ken Kuwahara, Ittetsu Kin, Michiari Umakoshi, Jun Morimoto, Mihoko Okazaki, Tatsuya Sasaki, Isao Date

    World neurosurgery   113   e391-e398   2018年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Optimal placement of electrodes is important for spinal cord stimulation. Factors affecting the difficulty of percutaneous electrode placement are not well known. In this study, we retrospectively evaluated the factors affecting the difficulty of percutaneous electrode placement. METHODS: We performed a retrospective analysis of 90 consecutive procedures of percutaneous cylindrical electrode implantation at the first author's institution. Age, sex, smoking state, body mass index, the duration of time from the beginning of pain syndrome to operation, diagnosis, the number of previous electrode placements, the previous electrode implantation period, the presence of axial low back pain, the electrode tip level, the pattern of electrode placement, and the reason for reimplantation were selected as factors associated with the success of electrode placement or the operation time of electrode placement. RESULTS: The number of previous electrode placements and the electrode tip level were independently associated with the operation time of electrode placement. According to both univariable and multivariable regression analyses, 1 previous electrode placement lengthened the operation time by approximately 15 minutes. No factors were significantly associated with the success of electrode placement. The more frequently that previous electrode placement was performed, the more difficult electrode placement tended to be. However, electrode reimplantation can be successful given extra time. CONCLUSIONS: This is the first study to evaluate factors affecting the difficulty of percutaneous electrode placement. A history of percutaneous cylindrical electrode placement did not affect the success of current placement, although it lengthened the operation time.

    DOI: 10.1016/j.wneu.2018.02.040

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  • 高齢者パーキンソン病に対する脳深部刺激療法─review─ 査読

    佐々木達也、安原隆雄、亀田雅博、上利 崇、伊達 勲

    Geriatric Neurosurgery   30   47 - 51   2018年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Spinal Extradural Arachnoid Cyst: Significance of Intrathecal Infusion after Fistula Closure.

    Michiari Umakoshi, Takao Yasuhara, Atsuhiko Toyoshima, Susumu Sasada, Akira Kusumegi, Jun Morimoto, Kyohei Kin, Yousuke Tomita, Isao Date

    Acta medica Okayama   72 ( 1 )   73 - 76   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The spinal extradural arachnoid cyst is a rare entity. Obtaining the correct diagnosis and detecting the fistula location are critical for providing effective treatment. A 41-year-old man had numbness in the soles of his feet for 2 years with accompanying gait disturbance, and a defecation disorder. Computed tomography myelography performed at another hospital revealed an epidural arachnoid cyst from Th11 to L2. He received a subarachnoid-cyst shunt at the rostral part of the cyst. However, his symptoms worsened and he was admitted to our hospital. Neuroradiological investigations revealed the correct location of the fistula at the level of Th12. We performed partial removal of the cyst wall with fistula closure via right hemilaminectomy of Th11 and 12. The complete closure of the fistula was confirmed by intrathecal infusion of artificial cerebrospinal fluid through the shunt tube. The shunt tube was removed with the sutures. The patient's symptoms improved, although numbness remained in his bilateral heels. There has been no recurrence in 15 months since the surgery. Fistula closure may work as a balanced therapeutic strategy for spinal extradural arachnoid cyst, and intrathecal cerebrospinal fluid infusion is useful for the confirmation of complete fistula closure.

    DOI: 10.18926/AMO/55666

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  • Neurolymphomatosis in the Cauda Equina Diagnosed by an Open Biopsy

    Ryo Sasaki, Yasuyuki Ohta, Yuto Yamada, Koh Tadokoro, Yoshiaki Takahashi, Kota Sato, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Takao Yasuhara, Isao Date, Shuntaro Ikegawa, Nobuharu Fujii, Koji Abe

    INTERNAL MEDICINE   57 ( 23 )   3463 - 3465   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    Neurolymphomatosis is a rare form of extranodal malignant lymphoma defined as the infiltration of malignant lymphocytes into the central or peripheral nerve. We herein report a case of neurolymphomatosis in the cauda equina diagnosed by an open surgical biopsy. He presented with muscle weakness, atrophy, numbness and hypoesthesia in the bilateral lower extremities with the accumulation of (18)fluoro-2-deoxyglucose (FDG) in the bilateral cauda equina. Cerebrospinal fluid cytology (three times) and flow cytometry (two times) and biopsies of the left rural nerve, bone marrow, paranasal sinus and left testis were all negative for malignancy, so finally we performed a surgical open biopsy of the cauda equina by laminectomy and diagnosed him with diffuse large B-cell lymphoma in the cauda equina. He was successfully treated with the disappearance of the FDG accumulation for a long time. The present case suggested that an early open biopsy of the cauda equina may be considered for cases of suspected neurolymphomatosis in the cauda equina for a good outcome.

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  • Long-Term Potentiation Enhances Neuronal Differentiation in the Chronic Hypoperfusion Model of Rats. 国際誌

    Hayato Takeuchi, Masahiro Kameda, Takao Yasuhara, Tatsuya Sasaki, Atsuhiko Toyoshima, Jun Morimoto, Kyohei Kin, Mihoko Okazaki, Michiari Umakoshi, Ittetsu Kin, Ken Kuwahara, Yosuke Tomita, Isao Date

    Frontiers in aging neuroscience   10   29 - 29   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several reports have shown that long-term potentiation (LTP) per se effectively enhances neurogenesis in the hippocampus of intact animals. If LTP can enhance neurogenesis in chronic hypoperfusion, this approach could potentially become a new therapeutic strategy for the restoration of cognitive function and for prevention from deterioration of mild cognitive impairment (MCI). Using an in vivo LTP model of rats, we examined whether LTP per se can enhance neurogenesis in hypoperfusion rats that underwent permanent bilateral common carotid artery occlusion (permanent 2-vessel occlusion, P2VO). High frequency stimulation (HFS) in the subacute phase after P2VO enhanced hippocampal cell proliferation and neurogenesis. However, most enhanced cell proliferation and neurogenesis was seen in the hypoperfusion rats that received HFS and for which LTP could finally be induced. In contrast, the same effect was not seen in the LTP induction in the chronic phase. The present findings, which reveal that most enhanced neurogenesis was seen in hypoperfusion rats for which LTP could be finally induced, could explain the ability of LTP-like activities such as learning paradigms and environmental stimuli to increase the rate of neurogenesis in the hippocampus even under hypoperfusion conditions. Moreover, the present findings, which reveal that LTP induction in the chronic phase after P2VO could not effectively enhance neurogenesis in the hypoperfusion rats, could indicate that patients with MCI and even middle-aged healthy control individuals should start LTP-like activities as early as possible and continue with these activities to prevent age-related deterioration of hippocampal function.

    DOI: 10.3389/fnagi.2018.00029

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  • 非もやもや病小児脳梗塞・脳虚血症例の治療におけるチーム医療の重要性

    安原 隆雄, 菱川 朋人, 亀田 雅博, 平松 匡文, 杉生 憲志, 野坂 宜之, 塚原 紘平, 八代 将登, 林 裕美子, 伊達 勲

    脳卒中の外科   45 ( 6 )   476 - 482   2017年11月

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    記述言語:日本語   出版者・発行元:(一社)日本脳卒中の外科学会  

    症例1:9歳女児。左片麻痺で発症し、右内包後脚脳梗塞と診断された。aspirin内服を行い、24ヵ月再発なく外来加療中である。症例2:13歳男児。けいれん発作、意識障害、左片麻痺が生じ、動脈炎として加療開始された。右中大脳動脈領域に脳梗塞を認めたため外減圧術を施行したが、第62病日に頭蓋骨形成術を施行後に意識障害が生じ、けいれん重積状態となった。barbitalを用いた2週間にわたる鎮静・呼吸循環管理にて徐々に改善したが、左不全麻痺の悪化、右不全麻痺を生じた。17ヵ月経過現在、両杖をついた歩行訓練を行っている。症例3:10ヵ月女児。左不全片麻痺で発症し、3日後に意識障害が生じた。右側の血栓性脳梗塞と考えaspirin内服を開始したが、脳梗塞の再発、左側に新規の脳梗塞を来たした。warfarinとaspirinの内科加療を開始し、16ヵ月再発なく経過している。症例4:2歳女児。Klippel-Trenaunay症候群として経過観察されていた。繰り返す左片麻痺とけいれん発作が生じ、右内頸動脈の閉塞ないし狭窄に伴う脳虚血と診断し、aspirin内服加療を開始した。16ヵ月間再発なく経過している。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J02079&link_issn=&doc_id=20171211180009&doc_link_id=%2Fcp4strok%2F2017%2F004506%2F009%2F0476-0482%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcp4strok%2F2017%2F004506%2F009%2F0476-0482%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Cell Therapy for Parkinson's Disease. 国際誌

    Takao Yasuhara, Masahiro Kameda, Tatsuya Sasaki, Naoki Tajiri, Isao Date

    Cell transplantation   26 ( 9 )   1551 - 1559   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cell therapy for Parkinson's disease (PD) began in 1979 with the transplantation of fetal rat dopamine-containing neurons that improved motor abnormalities in the PD rat model with good survival of grafts and axonal outgrowth. Thirty years have passed since the 2 clinical trials using cell transplantation for PD patients were first reported. Recently, cell therapy is expected to develop as a realistic treatment option for PD patients owing to the advancement of biotechnology represented by pluripotent stem cells. Medication using levodopa, surgery including deep brain stimulation, and rehabilitation have all been established as current therapeutic strategies. Strong therapeutic effects have been demonstrated by these treatment methods, but they have been unable to stop the progression of the disease. Fortunately, cell therapy might be a key for true neurorestoration. This review article describes the historical development of cell therapy for PD, the current status of cell therapy, and the future direction of this treatment method.

    DOI: 10.1177/0963689717735411

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  • Efficacy of Fiber Tractography in the Stereotactic Surgery of the Thalamus for Patients with Essential Tremor.

    Susumu Sasada, Takashi Agari, Tatsuya Sasaki, Akihiko Kondo, Aiko Shinko, Takaaki Wakamori, Mihoko Okazaki, Ittetsu Kin, Ken Kuwahara, Masahiro Kameda, Takao Yasuhara, Isao Date

    Neurologia medico-chirurgica   57 ( 8 )   392 - 401   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several targets and targeting methods are utilized in stereotactic surgery to achieve tremor suppression for patients with intractable tremor. Recent developments in magnetic resonance imaging, including diffusion tensor imaging, have enabled the setting of appropriate targets in stereotactic surgery. In this retrospective study, the optimal target to suppress tremors in stereotactic surgery was explored using diffusion tensor image-based fiber tractography. Four tracts were focused on in this study, namely: the cerebello-thalamo-premotor cortical fiber tract, cerebello-thalamo-primary motor cortical fiber tract, spino-thalamo-somatosensory cortical fiber tract, and pyramidal tract. In 10 patients with essential tremor, we evaluated the thalamotomy lesions and active contacts of the lead in thalamic stimulation by diffusion tensor image-based fiber tractography to reveal which part of the cerebral cortex is most affected by stereotactic surgery. Tremor suppression and adverse events were also evaluated in the patients involved in this study. Consequently, the good tremor suppression was achieved in all patients. There had been no permanent adverse events 3 months after surgery. Twelve lesions in thalamotomy patients or active contacts of the lead in thalamic stimulation patients were on the cerebello-thalamo-premotor cortical fiber tract (12/14 lesions or active contacts: 86%). In conclusion, the cerebello-thalamo-premotor cortical fiber tract may be an optimal target for tremor suppression. Diffusion tensor image-based fiber tractography may enable us to both determine the optimal target to achieve strong tremor suppression and to reduce the number of adverse events by keeping lesions or electrodes away from important fiber tracts, such as the pyramidal tract and spinothalamic fibers.

    DOI: 10.2176/nmc.oa.2016-0277

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  • Mesenchymal Stem Cell Therapy for Ischemic Stroke.

    Atsuhiko Toyoshima, Takao Yasuhara, Isao Date

    Acta medica Okayama   71 ( 4 )   263 - 268   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    To date, many animal studies have indicated the neuroprotective effects of mesenchymal stem cell (MSC) transplantation in ischemic stroke. Several clinical studies have also revealed the safety, feasibility, and neuroprotective effects in ischemic stroke patients. In this review, we present the main approaches of MSC transplantation in ischemic stroke, the mechanisms of MSC therapy, and the current clinical studies on MSC transplantation in ischemic stroke patients. We also explore the safety of MSC transplantation and conclude that MSC therapy will play an important role in the future treatment of ischemic stroke. The optimal timing, approach, and cell dose in the transplantation are important issues for successful clinical application.

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  • Hippocampal neurogenesis of Wistar Kyoto rats is congenitally impaired and correlated with stress resistance. 国際誌

    Kyohei Kin, Takao Yasuhara, Masahiro Kameda, Takashi Agari, Tatsuya Sasaki, Jun Morimoto, Mihoko Okazaki, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoki Tajiri, Isao Date

    Behavioural brain research   329   148 - 156   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The hippocampus is thought to be an important region for depression. However, the relationship between hippocampal neurogenesis and depression is still controversial. Wistar Kyoto (WKY) rats are frequently used as a depression model. WKY rats are known to show physiologically abnormal features, and these features resemble abnormalities seen in depressed patients. However, the neurogenesis of WKY rats is still unknown. In this study, we first evaluated the neurogenesis of WKY rats and compared it to that of Wistar (WIS) rats. No strain effect was observed in the number of cells positive for 5-bromo-2'-deoxyuridine (BrdU) and BrdU/Doublecortin (Dcx) in the subventricular zone (SVZ). However, the number of BrdU- and BrdU/Dcx-positive cells in the dentate gyrus (DG) of the hippocampus was significantly lower in WKY rats than in WIS rats. Next, we evaluated the correlation between neurogenesis and behavior tests. Behavior tests did not affect neurogenesis in either strain. Hippocampal neurogenesis correlated negatively with the results of a forced swim test (FST) on day 2 in each strain. That is, rats with a lower level of native neurogenesis in the DG showed a higher level of learned helplessness induced by the inescapable stress of the FST on day 1. Our findings indicate that hippocampal neurogenesis in WKY rats is congenitally impaired in contrast to that in WIS rats. Native cell proliferation and neurogenesis in the DG are correlated with stress resistance. These findings may be useful for developing new targets for depression treatment.

    DOI: 10.1016/j.bbr.2017.04.046

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  • Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy.

    Nobuyuki Nosaka, Kohei Tsukahara, Emily Knaup, Toshihiko Yabuuchi, Tomonobu Kikkawa, Yosuke Fujii, Masato Yashiro, Takao Yasuhara, Ayumi Okada, Toyomu Ugawa, Atsunori Nakao, Hirokazu Tsukahara, Isao Date

    Acta medica Okayama   71 ( 2 )   179 - 180   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management.

    DOI: 10.18926/AMO/54987

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  • リハビリテーションが神経保護・神経新生を増幅する

    安原 隆雄, 亀田 雅博, 菱川 朋人, 伊達 勲

    脳卒中   39 ( 5 )   396 - 399   2017年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本脳卒中学会  

    <p>リハビリテーションは脳卒中患者が良好な機能回復から社会復帰に至るまで,不可欠な治療の一つであると言える.このミニレビューでは,我々の研究室における2 つのリハビリに関連した研究,すなわち,パーキンソン病モデルラットにおけるリハビリテーションの神経保護効果と後肢懸垂による廃用症候群モデルラットにおける神経新生について成果を報告し,脳卒中患者に対するリハビリテーションの意義について,再生医療の観点から将来展望を交えて述べる.</p>

    DOI: 10.3995/jstroke.10482

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  • Surgery in the Standing Position by a Surgeon with Achilles Tendon Rupture.

    Takao Yasuhara, Ken Kuwahara, Susumu Sasada, Atsuhiko Toyoshima, Jun Morimoto, Kyohei Kin, Hiroaki Manabe, Yasuyuki Miyoshi, Akira Kusumegi, Yuichi Takahashi, Kiyoshi Ito, Isao Date

    Acta medica Okayama   70 ( 6 )   493 - 496   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Unexpected injuries can have a profound effect on a surgeon's performance and thus on patients and surgical departments. Here we describe a technique for performing surgery in the standing position, as done by a surgeon with an Achilles tendon rupture. During his prescribed 45-day non-weight-bearing period for the left ankle after surgery for an Achilles tendon rupture, the surgeon was able to participate in 15 surgeries as an operator or assistant, due to his use of a combination of injured-leg genuflection on a stool and a 'Surgical Body Support' device. Similarly injured surgeons may benefit from such support.

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  • Accuracy of Percutaneous Pedicle Screw Insertion Technique with Conventional Dual Fluoroscopy Units and a Retrospective Comparative Study Based on Surgeon Experience. 国際誌

    Masayuki Nakahara, Takao Yasuhara, Takafumi Inoue, Yuichi Takahashi, Shinji Kumamoto, Yasukazu Hijikata, Akira Kusumegi, Yushi Sakamoto, Koichi Ogawa, Kenki Nishida

    Global spine journal   6 ( 4 )   322 - 8   2016年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Study Design Retrospective comparative study. Objective To evaluate the accuracy of percutaneous pedicle screw (PPS) placement and intraoperative imaging time using dual fluoroscopy units and their differences between surgeons with more versus less experience. Methods One hundred sixty-one patients who underwent lumbar fusion surgery were divided into two groups, A (n = 74) and B (n = 87), based on the performing surgeon's experience. The accuracy of PPS placement and radiation time for PPS insertion were compared. PPSs were inserted with classic technique under the assistance of dual fluoroscopy units placed in two planes. The breach definition of PPS misplacement was based on postoperative computed tomography (grade I: no breach; grade II: <2 mm; grade III: ≤2 to <4 mm). Results Of 658 PPSs, only 21 screws were misplaced. The breach rates of groups A and B were 3.3% (grade II: 3.4%, grade III: 0%) and 3.1% (grade II: 2.6%, grade III: 0.6%; p = 0.91). One patient in grade III misplacement had a transient symptom of leg numbness. Median radiation exposure time during PPS insertion was 25 seconds and 51 seconds, respectively (p < 0.01). Conclusions Without using an expensive imaging support system, the classic technique of PPS insertion using dual fluoroscopy units in the lumbar and sacral spine is fairly accurate and provides good clinical outcomes, even among surgeons lacking experience.

    DOI: 10.1055/s-0035-1563405

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  • A Case of Unexpected Symptomatic Vasospasm after Clipping Surgery for an Unruptured Intracranial Aneurysm 査読 国際誌

    Hiroaki Hashimoto, Masahiro Kameda, Takao Yasuhara, Isao Date

    JOURNAL OF STROKE & CEREBROVASCULAR DISEASES   25 ( 3 )   E25 - E27   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Delayed symptomatic vasospasm after clipping surgery for unruptured aneurysm is rarely reported. We report a case of a 62-year-old woman who presented with symptomatic vasospasm 11 days after clipping surgery for an unruptured aneurysm. We could not predict the existence of vasospasm until ischemic symptoms developed. We retrospectively found mild vasospasm in the computed tomography angiogram taken 8 days after the operation. The patient complained of a prolonged unexpected headache 1 week after the operation. We should recognize prolonged unexpected headache as a warning sign of vasospasm.

    DOI: 10.1016/j.jstrokecerebrovasdis.2015.11.029

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  • Anti-high mobility group box 1 antibody exerts neuroprotection in a rat model of Parkinson's disease. 国際誌

    Tatsuya Sasaki, Keyue Liu, Takashi Agari, Takao Yasuhara, Jun Morimoto, Mihoko Okazaki, Hayato Takeuchi, Atsuhiko Toyoshima, Susumu Sasada, Aiko Shinko, Akihiko Kondo, Masahiro Kameda, Ikuko Miyazaki, Masato Asanuma, Cesario V Borlongan, Masahiro Nishibori, Isao Date

    Experimental neurology   275 Pt 1   220 - 31   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The high mobility group box-1 (HMGB1) exists as an architectural nuclear protein in the normal state, but displays an inflammatory cytokine-like activity in the extracellular space under pathological condition. Inflammation in the pathogenesis of Parkinson's disease (PD) has been documented. In this study, we investigated the involvement of HMGB1 in the pathology and the neuroprotective effects of neutralizing anti-HMGB1 monoclonal antibody (mAb) on an animal model of PD. Adult female Sprague-Dawley rats were initially injected with 6-hydroxydopmaine (6-OHDA, 20 μg/4 μl) into the right striatum, then anti-HMGB1 mAb (1 mg/kg), or control mAb was intravenously administered immediately, at 6 and 24 h after 6-OHDA injection. The treatment with anti-HMGB1 mAb significantly preserved dopaminergic neurons in substantia nigra pars compacta and dopaminergic terminals inherent in the striatum, and attenuated PD behavioral symptoms compared to the control mAb-treated group. HMGB1 was retained in the nucleus of neurons and astrocytes by inhibiting the proinflammation-induced oxidative stress in the anti-HMGB1 mAb-treated group, whereas HMGB1 translocation was observed in neurons at 1 day and astrocytes at 7 days after 6-OHDA injection in the control mAb-treated group. Anti-HMGB1 mAb inhibited the activation of microglia, disruption of blood-brain-barrier (BBB), and the expression of inflammation cytokines such as IL-1β and IL-6. These results suggested that HMGB1 released from neurons and astrocytes was at least partly involved in the mechanism and pathway of degeneration of dopaminergic neurons induced by 6-OHDA exposure. Intravenous administration of anti-HMGB1 mAb stands as a novel therapy for PD possibly acting through the suppression of neuroinflammation and the attenuation of disruption of BBB associated with the disease.

    DOI: 10.1016/j.expneurol.2015.11.003

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  • Perioperative Management Center (PERIO) for Neurosurgical Patients 査読

    Takao Yasuhara, Tomohito Hishikawa, Takashi Agari, Kazuhiko Kurozumi, Tomotsugu Ichikawa, Masahiro Kameda, Aiko Shinko, Joji Ishida, Masafumi Hiramatsu, Motomu Kobayashi, Yoshikazu Matsuoka, Toshihiro Sasaki, Yoshihiko Soga, Reiko Yamanaka, Takako Ashiwa, Akemi Arioka, Yasuko Hashimoto, Ayasa Misaki, Yuriko Ishihara, Machiko Sato, Hiroshi Morimatsu, Isao Date

    NEUROLOGIA MEDICO-CHIRURGICA   56 ( 9 )   574 - 579   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN NEUROSURGICAL SOC  

    Perioperative management is critical for positive neurosurgical outcomes. In order to maintain safe and authentic perioperative management, a perioperative management center (PERIO) was introduced to patients of our Neurosurgery Department beginning in June 2014. PERIO involves a multidisciplinary team consisting of anesthesiologists, dentists/dental hygienists/technicians, nurses, physical therapists, pharmacists, and nutritionists. After neurosurgeons decide on the course of surgery, a preoperative evaluation consisting of blood sampling, electrocardiogram, chest X-ray, and lung function test was performed. The patients then visited the PERIO clinic 7-14 days before surgery. One or two days before surgery, the patients without particular issues enter the hospital and receive a mouth cleaning one day before surgery. After surgery, postoperative support involving eating/swallowing evaluation, rehabilitation, and pain control is provided. The differences in duration from admission to surgery, cancellation of surgery, and postoperative complications between PERIO and non-PERIO groups were examined. Eighty-five patients were enrolled in the PERIO group and 131 patients in the non-PERIO group. The duration from admission to surgery was significantly decreased in the PERIO group (3.6 +/- 0.3 days), compared to that in the non-PERIO group (4.7 +/- 0.2 days). There was one cancelled surgery in the PERIO group and six in the non-PERIO group. Postoperative complications and the overall hospital stay did not differ between the two groups. The PERIO system decreased the duration from admission to surgery, and it is useful in providing high-quality medical service, although the system should be improved so as not to increase the burden on medical staff.

    DOI: 10.2176/nmc.oa.2016-0085

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  • Superior ophthalmic vein thrombosis associated with severe facial trauma: a case report. 査読 国際誌

    Mishima M, Yumoto T, Hashimoto H, Yasuhara T, Iida A, Tsukahara K, Sato K, Ugawa T, Otsuka F, Ujike Y

    Journal of medical case reports   9   244 - 244   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1186/s13256-015-0737-y

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  • [Cervical spinal dural arteriovenous fistula with rapidly progressive brainstem dysfunction due to venous congestion: a case report].

    Tatsuya Sasaki, Hiroaki Manabe, Takao Yasuhara, Yasuyuki Miyoshi, Kenji Sugiu, Isao Date

    No shinkei geka. Neurological surgery   43 ( 1 )   51 - 6   2015年1月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Spinal dural arteriovenous fistulas(S-dAVFs)are rare vascular malformations of the spine. We experienced a case that presented with rapidly progressive brainstem dysfunction due to venous congestion of cervical dAVFs. A 56-year-old man diagnosed with cervical dAVF four years prior presented with gait disturbance and abnormal thermal nociception on his right side. In addition to the high-intensity lesion from the lower pons to the medulla oblongata on T2-weighted magnetic resonance imaging, diffusion-weighted imaging demonstrated cerebral infarction of the left ventrolateral medulla oblongata. Left vertebral angiography revealed that a feeding artery supplied by the radicular artery at the C4 level formed a fistula with the dilated ascending anterior perimedullary vein. We made a diagnosis of venous congestion due to cervical dAVFs. Numbness on the left upper limb occurred five days after the first symptom. Subsequently, hemiparesis on the left upper limb and swallowing disturbance occurred two weeks after the first symptom. The patient underwent surgical ligation of the dilated abnormal vein, with gradual improvement of his symptoms. Myelopathy due to venous congestion of S-dAVFs usually progresses slowly for several years. However, this case report warns about the possibility that some cases of S-dAVF with rapidly exacerbated symptoms may require prompt therapy.

    DOI: 10.11477/mf.1436202944

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  • Regenerative medicine for Parkinson's disease.

    Takao Yasuhara, Masahiro Kameda, Takashi Agari, Isao Date

    Neurologia medico-chirurgica   55 ( 2 )   113 - 23   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Regenerative medicine for Parkinson's disease (PD) is expected to develop dramatically with the advancement of biotechnology as represented by induced pluripotent stem cells. Existing therapeutic strategy for PD consists of medication using L-DOPA, surgery such as deep brain stimulation and rehabilitation. Current treatment cannot stop the progression of the disease, although there is definite therapeutic effect. True neurorestoration is strongly desired by regenerative medicine. This review article describes the historical development of regenerative medicine for PD, with a focus on fetal nigral cell transplantation and glial cell line-derived neurotrophic factor infusion. Subsequently, the current status of regenerative medicine for PD in terms of cell therapy and gene therapy are reviewed. In the end, the future direction to realize regenerative medicine for PD is discussed.

    DOI: 10.2176/nmc.ra.2014-0264

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  • Intra-Arterial Transplantation of Allogeneic Mesenchymal Stem Cells Mounts Neuroprotective Effects in a Transient Ischemic Stroke Model in Rats: Analyses of Therapeutic Time Window and Its Mechanisms. 国際誌

    Atsuhiko Toyoshima, Takao Yasuhara, Masahiro Kameda, Jun Morimoto, Hayato Takeuchi, Feifei Wang, Tatsuya Sasaki, Susumu Sasada, Aiko Shinko, Takaaki Wakamori, Mihoko Okazaki, Akihiko Kondo, Takashi Agari, Cesario V Borlongan, Isao Date

    PloS one   10 ( 6 )   e0127302   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Intra-arterial stem cell transplantation exerts neuroprotective effects for ischemic stroke. However, the optimal therapeutic time window and mechanisms have not been completely understood. In this study, we investigated the relationship between the timing of intra-arterial transplantation of allogeneic mesenchymal stem cells (MSCs) in ischemic stroke model in rats and its efficacy in acute phase. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. MSCs (1 × 10(6) cells/ 1 ml PBS) were intra-arterially injected at either 1, 6, 24, or 48 hours (1, 6, 24, 48 h group) after MCAO. PBS (1 ml) was intra-arterially injected to control rats at 1 hour after MCAO. Behavioral test was performed immediately after reperfusion, and at 3, 7 days after MCAO using the Modified Neurological Severity Score (mNSS). Rats were euthanized at 7 days after MCAO for evaluation of infarct volumes and the migration of MSCs. In order to explore potential mechanisms of action, the upregulation of neurotrophic factor and chemotactic cytokine (bFGF, SDF-1α) induced by cell transplantation was examined in another cohort of rats that received intra-arterial transplantation at 24 hours after recanalization then euthanized at 7 days after MCAO for protein assays. RESULTS: Behavioral test at 3 and 7 days after transplantation revealed that stroke rats in 24h group displayed the most robust significant improvements in mNSS compared to stroke rats in all other groups (p's<0.05). Similarly, the infarct volumes of stroke rats in 24h group were much significantly decreased compared to those in all other groups (p's<0.05). These observed behavioral and histological effects were accompanied by MSC survival and migration, with the highest number of integrated MSCs detected in the 24h group. Moreover, bFGF and SDF-1α levels of the infarcted cortex were highly elevated in the 24h group compared to control group (p's<0.05). CONCLUSIONS: These results suggest that intra-arterial allogeneic transplantation of MSCs provides post-stroke functional recovery and reduction of infarct volumes in ischemic stroke model of rats. The upregulation of bFGF and SDF-1α likely played a key mechanistic role in enabling MSC to afford functional effects in stroke. MSC transplantation at 24 hours after recanalization appears to be the optimal timing for ischemic stroke model, which should guide the design of clinical trials of cell transplantation for stroke patients.

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  • Regenerative Medicine for Parkinson’s Disease.

    Takao Yasuhara, Masahiro Kameda, Takashi Agari, Isao Date

    Neurologia medico-chirurgica   55 Suppl 1 ( 2 )   113 - 23   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Regenerative medicine for Parkinson’s disease (PD) is expected to develop dramatically with the advancement of biotechnology as represented by induced pluripotent stem cells. Existing therapeutic strategy for PD consists of medication using L-DOPA, surgery such as deep brain stimulation and rehabilitation. Current treatment cannot stop the progression of the disease, although there is definite therapeutic effect. True neurorestoration is strongly desired by regenerative medicine. This review article describes the historical development of regenerative medicine for PD, with a focus on fetal nigral cell transplantation and glial cell line-derived neurotrophic factor infusion. Subsequently, the current status of regenerative medicine for PD in terms of cell therapy and gene therapy are reviewed. In the end, the future direction to realize regenerative medicine for PD is discussed.

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  • Cognitive functions in Parkinson's disease: Relation to disease severity and hallucination 査読 国際誌

    Takaaki Wakamori, Takashi Agari, Takao Yasuhara, Masahiro Kameda, Akihiko Kondo, Aiko Shinko, Susumu Sasada, Tatsuya Sasaki, Tomohisa Furuta, Isao Date

    PARKINSONISM & RELATED DISORDERS   20 ( 4 )   415 - 420   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Objective: We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF).
    Methods: Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF.
    Results: The mean MMSE score of PD patients was 27.4 +/- 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 +/- 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus.
    Conclusions: This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes. (C) 2014 Elsevier Ltd. All rights reserved.

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  • Spinal cord stimulation exerts neuroprotective effects against experimental Parkinson's disease. 国際誌

    Aiko Shinko, Takashi Agari, Masahiro Kameda, Takao Yasuhara, Akihiko Kondo, Judith Thomas Tayra, Kenichiro Sato, Tatsuya Sasaki, Susumu Sasada, Hayato Takeuchi, Takaaki Wakamori, Cesario V Borlongan, Isao Date

    PloS one   9 ( 7 )   e101468   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    In clinical practice, deep brain stimulation (DBS) is effective for treatment of motor symptoms in Parkinson's disease (PD). However, the mechanisms have not been understood completely. There are some reports that electrical stimulation exerts neuroprotective effects on the central nervous system diseases including cerebral ischemia, head trauma, epilepsy and PD, although there are a few reports on neuroprotective effects of spinal cord stimulation (SCS). We investigated the neuroprotective effects of high cervical SCS on PD model of rats. Adult female Sprague-Dawley rats received hour-long SCS (2, 50 or 200 Hz) with an epidural electrode at C1-2 level for 16 consecutive days. At 2 days after initial SCS, 6-hydroxydopamine (6-OHDA) was injected into the right striatum of rats. Behavioral evaluations of PD symptoms were employed, including cylinder test and amphetamine-induced rotation test performed at 1 and 2 weeks after 6-OHDA injection. Animals were subsequently euthanized for immunohistochemical investigations. In order to explore neurotrophic and growth factor upregulation induced by SCS, another cohort of rats that received 50 Hz SCS was euthanized at 1 and 2 weeks after lesion for protein assays. Behavioral tests revealed that the number of amphetamine-induced rotations decreased in SCS groups. Immunohistochemically, tyrosine hydroxylase (TH)-positive fibers in the striatum were significantly preserved in SCS groups. TH-positive neurons in the substantia nigra pars compacta were significantly preserved in 50 Hz SCS group. The level of vascular endothelial growth factor (VEGF) was upregulated by SCS at 1 week after the lesion. These results suggest that high cervical SCS exerts neuroprotection in PD model of rats, at least partially by upregulation of VEGF. SCS is supposed to suppress or delay PD progression and might become a less invasive option for PD patients, although further preclinical and clinical investigations are needed to confirm the effectiveness and safety.

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  • Neuroprotective effects of liraglutide for stroke model of rats. 国際誌

    Kenichiro Sato, Masahiro Kameda, Takao Yasuhara, Takashi Agari, Tanefumi Baba, Feifei Wang, Aiko Shinko, Takaaki Wakamori, Atsuhiko Toyoshima, Hayato Takeuchi, Tatsuya Sasaki, Susumu Sasada, Akihiko Kondo, Cesario V Borlongan, Mitsunori Matsumae, Isao Date

    International journal of molecular sciences   14 ( 11 )   21513 - 24   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The number of diabetes mellitus (DM) patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1) are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson's test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF). The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

    DOI: 10.3390/ijms141121513

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  • Mannitol enhances therapeutic effects of intra-arterial transplantation of mesenchymal stem cells into the brain after traumatic brain injury. 国際誌

    Yu Okuma, Feifei Wang, Atsuhiko Toyoshima, Masahiro Kameda, Tomohito Hishikawa, Koji Tokunaga, Kenji Sugiu, Keyue Liu, Jun Haruma, Masahiro Nishibori, Takao Yasuhara, Isao Date

    Neuroscience letters   554   156 - 61   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major cause of death that affects a broad range of ages. The aim of this study was to investigate the therapeutic effects of intra-arterial transplantation of mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol (25%) in a TBI model of rats. TBI models were produced with a fluid percussion device. At 24h after TBI, MSCs (1×10(6)cells/100μl) with glycerol or mannitol were administered via the right internal carotid artery. Rats were evaluated behaviorally and immunohistochemically, and hyperpermeability of the blood-brain barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or glycerol, the administration of mannitol resulted in increased BBB disruption. The mannitol-treated rats showed significant improvement in motor function. Intra-arterial transplantation of MSCs caused no thromboembolic ischemia. Immunohistochemically, more MSCs were observed in the injured brain tissues of mannitol-treated rats than in glycerol or PBS-treated rats at 24h after transplantation. Intra-arterial transplantation of MSCs combined with mannitol is an effective treatment in a TBI model of rats. This technique might be used for patients with diseases of the central nervous system including TBI.

    DOI: 10.1016/j.neulet.2013.08.058

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  • The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. 国際誌

    Judith Thomas Tayra, Masahiro Kameda, Takao Yasuhara, Takashi Agari, Tomohito Kadota, Feifei Wang, Yoichiro Kikuchi, Hanbai Liang, Aiko Shinko, Takaaki Wakamori, Brigitta Vcelar, Robert Weik, Isao Date

    Brain research   1502   55 - 70   2013年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons. Thus the development of therapeutic neuroprotection and neurorescue strategies to mitigate disease progression is important. In this study we evaluated the neuroprotective/rescue effects of erythropoietin Fc fusion protein (EPO-Fc) and carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson's disease. Adult female Sprague-Dawley rats received intraperitoneal injection of EPO-Fc, CEPO-Fc or PBS. Behavioral evaluations consisted of rota-rod, cylinder and amphetamine-induced rotation tests. In the neuroprotection experiment, the CEPO-Fc group demonstrated significant improvement compared with the EPO-Fc group on the amphetamine-induced rotation test throughout the four-week follow-up period. Histologically, significantly more tyrosine hydroxylase (TH)-positive neurons were recognized in the substantia nigra (SN) pars compacta in the CEPO-Fc group than in the PBS and EPO-Fc groups. In the neurorescue experiment, rats receiving CEPO-Fc showed significantly better behavioural scores than those receiving PBS. The histological data concerning striatum also showed that the CEPO-Fc group had significantly better preservation of TH-positive fibers compared to the PBS and EPO-Fc groups. Importantly, there were no increases in hematocrit or hemoglobin levels in the CEPO-Fc group in either the neuroprotection or the neurorescue experiments. In conclusion, the newly developed CEPO-Fc might confer neuroprotective and neurorescue benefits in a rat model of Parkinson's disease without the side effects associated with polycythemia. CEPO-Fc might be a therapeutic tool for patients with Parkinson's disease.

    DOI: 10.1016/j.brainres.2013.01.042

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  • Laterality of cervical disc herniation. 国際誌

    Yuichi Takahashi, Takao Yasuhara, Shinji Kumamoto, Kotaro Yoneda, Takashi Tanoue, Masayuki Nakahara, Takafumi Inoue, Yasukazu Hijikata, Tejin Lee, Cesario V Borlongan, Koichi Ogawa, Kenki Nishida

    European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society   22 ( 1 )   178 - 82   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: Cervical disc herniation (CDH) is found more frequently at the lower cervical spine than at the upper or middle level. However, there is scarcity of data about the laterality of CDH. The aim of this study is to detect the laterality of CDH. METHODS: We retrospectively evaluated preoperative computed tomography myelograms and magnetic resonance images of 75 cases of CDH who underwent single level anterior cervical discectomy and fusion at C4-5, C5-6, or C6-7 levels from 2008 to 2010 in our institute. Statistical analyses were performed using the Chi-square test. RESULTS: Eleven cases were found at C4-5 level, 42 cases at C5-6 level, and 22 cases at C6-7 level. At C4-5 level, CDH was recognized at the right side in 2 cases, at the left side in 2 cases, and at the center in 7 cases. At C5-6 level, CDH was found at the right side in 20 cases and at the left side in 22 cases. At C6-7 level, CDH was found at the right side in 3 cases and at the left side in 19 cases with significantly high frequency of left-sided CDH (p < 0.025). CONCLUSIONS: In this study, it was revealed that the left-sided CDH was more frequent than the right-sided CDH at C6-7 level.

    DOI: 10.1007/s00586-012-2565-8

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  • Proximal vertebral body fracture after 4-level fusion using l1 as the upper instrumented vertebra for lumbar degenerative disease: report of 2 cases with literature review.

    Takao Yasuhara, Yuichi Takahashi, Shinji Kumamoto, Masayuki Nakahara, Kotaro Yoneda, Tatsuomi Niimura, Takashi Tanoue, Akira Kusumegi, Takashi Sennari, Yasukazu Hijikata, Hiroaki Manabe, Yasuyuki Miyoshi, Isao Date, Koichi Ogawa, Kenki Nishida

    Acta medica Okayama   67 ( 3 )   197 - 202   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Some cases with lumbar degenerative diseases require multi-level fusion surgeries. At our institute, 27 and 4 procedures of 3- and 4-level fusion were performed out of a total 672 posterior lumbar interfusions (PLIFs) on patients with lumbar degenerative disease from 2005 to 2010. We present 2 osteoporotic patients who developed proximal vertebral body fracture after 4-level fusion. Both cases presented with gait disability for leg pain by degenerative lumbar scoliosis and canal stenosis at the levels of L1/2-4/5. After 4-level fusion using L1 as the upper instrumented vertebra, proximal vertebral body fractures were found along with the right pedicle fractures of L1 in both cases. One of these patients, aged 82 years, was treated as an outpatient using a hard corset for 24 months, but the fractures were exacerbated over time. In the other patient, posterolateral fusion was extended from Th10 to L5. Both patients can walk alone and have been thoroughly followed up. In both cases, the fracture of the right L1 pedicle might be related to the subsequent fractures and fusion failure. In consideration of multi-level fusion, L1 should be avoided as an upper instrumented vertebra to prevent junctional kyphosis, especially in cases with osteoporosis and flat back posture.

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  • Overheated and melted intracranial pressure transducer as cause of thermal brain injury during magnetic resonance imaging: case report. 国際誌

    Reiichiro Tanaka, Tetsuya Yumoto, Naoki Shiba, Motohisa Okawa, Takao Yasuhara, Tomotsugu Ichikawa, Koji Tokunaga, Isao Date, Yoshihito Ujike

    Journal of neurosurgery   117 ( 6 )   1100 - 9   2012年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Magnetic resonance imaging is used with increasing frequency to provide accurate clinical information in cases of acute brain injury, and it is important to ensure that intracranial pressure (ICP) monitoring devices are both safe and accurate inside the MRI suite. A rare case of thermal brain injury during MRI associated with an overheated ICP transducer is reported. This 20-year-old man had sustained a severe contusion of the right temporal and parietal lobes during a motor vehicle accident. An MR-compatible ICP transducer was placed in the left frontal lobe. The patient was treated with therapeutic hypothermia, barbiturate therapy, partial right temporal lobectomy, and decompressive craniectomy. Immediately after MRI examination on hospital Day 6, the ICP monitor was found to have stopped working, and the transducer was subsequently removed. The patient developed meningitis after this event, and repeat MRI revealed additional brain injury deep in the white matter on the left side, at the location of the ICP transducer. It is suspected that this new injury was caused by heating due to the radiofrequency radiation used in MRI because it was ascertained that the tip of the transducer had been melted and scorched. Scanning conditions--including configuration of the transducer, MRI parameters such as the type of radiofrequency coil, and the specific absorption rate limit--deviated from the manufacturer's recommendations. In cooperation with the manufacturer, the authors developed a precautionary tag describing guidelines for safe MR scanning to attach to the display unit of the product. Strict adherence to the manufacturer's guidelines is very important for preventing serious complications in patients with ICP monitors undergoing MRI examinations.

    DOI: 10.3171/2012.9.JNS12738

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  • パーキンソン病モデルラットに対する間葉系幹細胞移植の治療効果

    王 飛霏, 安原 隆雄, 亀田 雅博, 伊達 勲

    岡山医学会雑誌   124 ( 2 )   111 - 114   2012年8月

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    記述言語:日本語   出版者・発行元:岡山医学会  

    DOI: 10.4044/joma.124.111

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  • The therapeutic potential of human umbilical cord blood transplantation for neonatal hypoxic-ischemic brain injury and ischemic stroke.

    Feifei Wang, Nagamasa Maeda, Takao Yasuhara, Masahiro Kameda, Emi Tsuru, Tatsuyuki Yamashita, Yuan Shen, Masayuki Tsuda, Isao Date, Yusuke Sagara

    Acta medica Okayama   66 ( 6 )   429 - 34   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Human umbilical cord blood (HUCB) cells are rich source of immature stem cells, which have the potential to repair lost tissue. Intractable central nervous system (CNS) disorders are important targets for regenerative medicine, and the application of HUCB cells is being investigated in animal models of CNS disorders. Transplantation of HUCB has induced functional improvements in these animal models due to multiple therapeutic effects including neuroprotection, anti-inflammation, angiogenesis, and neurogenesis. HUCB cells are easily available and safer than other stem cells used in transplantation therapy. In this review, we focus on HUCB transplantation as an encouraging therapeutic approach for animal models of neonatal hypoxic-ischemic brain injury and ischemic stroke.

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  • Multiple intracranial hemorrhages after cervical spinal surgery.

    Yuichi Takahashi, Kenki Nishida, Koichi Ogawa, Takao Yasuhara, Shinji Kumamoto, Tatsuomi Niimura, Takashi Tanoue

    Neurologia medico-chirurgica   52 ( 9 )   643 - 5   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 69-year-old woman presented with a rare case of multiple supra- and infratentorial intracranial hemorrhages after cervical laminoplasty for cervical spondylotic myelopathy without intraoperative liquorrhea. A wound drainage tube under negative pressure was placed with subsequent 380 ml of drainage in the first 12 hours. She had no complaint of headache and nausea at that time. Computed tomography of the brain obtained at 15 hours after surgery demonstrated cerebellar hemorrhage, acute subdural hemorrhage, subarachnoid hemorrhage, supratentorial intraparenchymal hemorrhage, and pneumocephalus. She was treated medically without consequent neurological deficits other than right hemianopsia. Overdrainage of cerebrospinal fluid through an occult dural tear might cause severely low intracranial pressure with subsequent multiple intracranial hemorrhages. Wound drainage should be controlled thoroughly even in patients without intraoperative liquorrhea.

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  • Urinary 8-OHdG elevations in a partial lesion rat model of Parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion. 国際誌

    Yoichiro Kikuchi, Takao Yasuhara, Takashi Agari, Akihiko Kondo, Satoshi Kuramoto, Masahiro Kameda, Tomohito Kadota, Tanefumi Baba, Naoki Tajiri, Feifei Wang, Judith T Tayra, Hanbai Liang, Yasuyuki Miyoshi, Cesario V Borlongan, Isao Date

    Journal of cellular physiology   226 ( 5 )   1390 - 8   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Increased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8-OHdG in PD patients. There are few basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). The urinary 8-OHdG level was measured in relation to behavioral and pathological deficits arising from 6-OHDA-induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6-OHDA injection. We collected urine samples with subsequent measurement of 8-OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8-OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8-OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8-OHdG level provides a good index of severity of parkinsonism. Urinary 8-OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6-OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8-OHdG level closely approximate onset and disease progression in PD.

    DOI: 10.1002/jcp.22467

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  • Effectiveness of intraoperative near-infrared indocyanine green videoangiography in a case with recurrent spinal perimedullary arteriovenous fistula. 国際誌

    Yasuyuki Miyoshi, Takao Yasuhara, Ayumi Nishida, Koji Tokunaga, Kenji Sugiu, Isao Date

    Clinical neurology and neurosurgery   113 ( 3 )   239 - 42   2011年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.clineuro.2010.10.014

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  • Posterior reversible encephalopathy syndrome. 国際誌

    Takao Yasuhara, Koji Tokunaga, Tomohito Hishikawa, Shigeki Ono, Yasuyuki Miyoshi, Kenji Sugiu, Isao Date

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   18 ( 3 )   406 - 9   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological entity with typical symptoms and symmetric high-signal intensity lesions in the bilateral parieto-occipital lobes on T2-weighted or fluid-attenuated inversion recovery (FLAIR) MRI. We described three patients with PRES of varied etiologies. Patient 1 was a young man with severe hypertension who presented with headache and visual disturbance. Patient 2 had leukemia and was receiving umbilical cord blood cell transplantation with immunosuppressant, and developed PRES with convulsions. Patient 3 was a pregnant woman with renal failure, who repeatedly developed PRES with convulsions. FLAIR and apparent diffusion coefficient mapping were useful in detecting PRES lesions in our patients, although diffusion-weighted imaging and CT scans had limited use in the diagnosis. Adequate and prompt treatment with antihypertensive medication immediately ameliorated the symptoms, with improvement of abnormal MRI findings. In previous reports, delayed diagnosis might have affected the prognosis. Further work on the clinical manifestations of PRES and its therapy is required.

    DOI: 10.1016/j.jocn.2010.06.011

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  • Chiari malformation with thick occipital bone.

    Takao Yasuhara, Yasuyuki Miyoshi, Isao Date

    Acta medica Okayama   65 ( 1 )   59 - 61   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A case of a Chiari malformation with an extraordinarily thick occipital bone is described. The thick occipital bone might make the posterior fossa narrow with consequent herniation of the cerebellar tonsils to the foramen magnum and formation of a syrinx. At dural plasty, well-developed marginal and occipital sinuses should be deliberately handled with the preservation of normal venous drainage. This case gives us the essence of the occurrence mechanisms of Chiari malformation and foramen magnum decompression.

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  • [Vasospasm of Adamkiewicz artery after subarachnoid hemorrhage].

    Yasuyuki Miyoshi, Akihiko Kondo, Takao Yasuhara, Ayumi Nishida, Koji Tokunaga, Kenji Sugiu, Isao Date

    Brain and nerve = Shinkei kenkyu no shinpo   63 ( 2 )   182 - 3   2011年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats. 国際誌

    Satoshi Kuramoto, Takao Yasuhara, Takashi Agari, Akihiko Kondo, Meng Jing, Yoichiro Kikuchi, Aiko Shinko, Takaaki Wakamori, Masahiro Kameda, Feifei Wang, Kyohei Kin, Satoru Edahiro, Yasuyuki Miyoshi, Isao Date

    Brain research   1368   281 - 9   2011年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Brain-derived neurotrophic factor (BDNF) is a well neurotrophic factor with neuroprotective potentials for various diseases in the central nervous system. However several previous studies demonstrated that BDNF might deteriorate symptoms for epilepsy model of animals by progression of abnormal neurogenesis. We hypothesized that continuous administration of BDNF at low dose might be more effective for epilepsy model of animals because high dose of BDNF was used in many studies. BDNF-secreting cells were genetically made and encapsulated for transplantation. Rats receiving BDNF capsule showed significant amelioration of seizure stage and reduction of the number of abnormal spikes at 7 days after kainic acid administration, compared to those of control group. The number of BrdU and BrdU/doublecortin positive cells in the hippocampus of BDNF group significantly increased, compared to that of control group. NeuN positive cells in the CA1 and CA3 of BDNF group were significantly preserved, compared to control group. In conclusion, low dose administration using encapsulated BDNF-secreting cells exerted neuroprotective effects with enhanced neurogenesis on epilepsy model of rats. These results might suggest the importance of the dose and administrative way of this neurotrophic factor to the epilepsy model of animals.

    DOI: 10.1016/j.brainres.2010.10.054

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  • Striatal stimulation nurtures endogenous neurogenesis and angiogenesis in chronic-phase ischemic stroke rats. 国際誌

    Takamasa Morimoto, Takao Yasuhara, Masahiro Kameda, Tanefumi Baba, Satoshi Kuramoto, Akihiko Kondo, Kazuya Takahashi, Naoki Tajiri, Feifei Wang, Jing Meng, Yuan Wen Ji, Tomohito Kadota, Tomoko Maruo, Kazushi Kinugasa, Yasuyuki Miyoshi, Tetsuro Shingo, Cesario V Borlongan, Isao Date

    Cell transplantation   20 ( 7 )   1049 - 64   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Deep brain stimulation (DBS) is used to treat a variety of neurological disorders including Parkinson's disease. In this study, we explored the effects of striatal stimulation (SS) in a rat model of chronic-phase ischemic stroke. The stimulation electrode was implanted into the ischemic penumbra at 1 month after middle cerebral artery occlusion (MCAO) and thereafter continuously delivered SS over a period of 1 week. Rats were evaluated behaviorally coupled with neuroradiological assessment of the infarct volumes using magnetic resonance imaging (MRI) at pre- and post-SS. The rats with SS showed significant behavioral recovery in the spontaneous activity and limb placement test compared to those without SS. MRI visualized that SS also significantly reduced the infarct volumes compared to that at pre-SS or without SS. Immunohistochemical analyses revealed a robust neurogenic response in rats that received SS characterized by a stream of proliferating cells from the subventricular zone migrating to and subsequently differentiating into neurons in the ischemic penumbra, which exhibited a significant GDNF upregulation. In tandem with this SS-mediated neurogenesis, enhanced angiogenesis was also recognized as revealed by a significant increase in VEGF levels in the penumbra. These results provide evidence that SS affords neurorestoration at the chronic phase of stroke by stimulating endogenous neurogenesis and angiogenesis.

    DOI: 10.3727/096368910X544915

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  • Posterior decompression of far-out foraminal stenosis caused by a lumbosacral transitional vertebra--case report.

    Yasuyuki Miyoshi, Takao Yasuhara, Isao Date

    Neurologia medico-chirurgica   51 ( 2 )   153 - 6   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 29-year-old man presented with a rare case of far-out foraminal stenosis with radiculopathy caused by osteophyte formation secondary to an anomalous articulation between the transverse process and the sacral ala. Diagnosis of unilateral far-out foraminal entrapment of the L5 spinal nerve below a transitional vertebra (TV) depended on selective radiculography and nerve root block. Computed tomography after selective radiculography clearly demonstrated foraminal entrapment of the L5 nerve root via the osteophytes. The patient underwent posterior decompression by resection of the osteophytes using an operating microscope and experienced good relief of radicular pain. This case illustrates the effectiveness and some refinements of posterior decompression for radicular pain caused by far-out foraminal stenosis below a TV and compression of the L5 spinal nerve.

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  • Primary germinoma in the medulla oblongata - case report - .

    Takao Yasuhara, Tomotsugu Ichikawa, Yasuyuki Miyoshi, Kazuhiko Kurozumi, Tomoko Maruo, Hiroyuki Yanai, Isao Date

    Neurologia medico-chirurgica   51 ( 4 )   326 - 9   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 27-year-old woman presented with a case of primary medulla oblongata germinoma manifesting as sleep apnea, aspiration pneumonia, and left hemiparesis. Magnetic resonance (MR) imaging revealed a dorsal mass in the medulla oblongata with heterogeneous enhancement by gadolinium (Gd). Emergent biopsy and foramen magnum decompression with C1 laminectomy were performed because of rapid worsening of her symptoms. The histological diagnosis was germinoma. Subsequently she received chemoradiation therapy with subsequent amelioration of her neurological deficits and disappearance of enhancement on MR imaging with Gd. Primary medulla oblongata germinoma is rare and difficult to diagnose preoperatively. However, correct diagnosis and subsequent adequate chemoradiation therapy is possible by understanding the common characteristics of the disease. Germinoma should be included in the differential diagnosis of midline medullary lesion in young patients, and biopsy should be considered.

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  • Noonan syndrome with occipito-atlantal dislocation and upper cervical cord compression due to C1 dysplasia and basilar invagination.

    Yasuyuki Miyoshi, Takao Yasuhara, Isao Date

    Neurologia medico-chirurgica   51 ( 6 )   463 - 6   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 11-year-old female with Noonan syndrome presented with occipito-atlantal dislocation and upper cervical cord compression due to C1 dysplasia and basilar invagination. Computed tomography (CT) of the cervical spine showed dysplasia of the C1 posterior arch and bilateral dislocation of the occipito-atlantal joints. Dynamic lateral radiography revealed no instability at the occipito-atlantal joints. CT also demonstrated basilar invagination. The tip of the odontoid process extended above the Chamberlain line by 9 mm and the McGregor line by 10 mm. Whole spinal radiography showed no scoliosis. C1 laminectomy was performed with instrumented occipito-C2 fixation. The postoperative course was uneventful, and magnetic resonance imaging revealed sufficient decompression of the upper cervical cord at 2 months after surgery. CT demonstrated solid bony fusion between the occipital bone and C2 at 8 months after surgery. Cervical neuraxial malformations are rare in patients with Noonan syndrome.

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  • Development of cervical subarachnoid hematoma following coronal artery stenting for angina pectoris.

    Takao Yasuhara, Yasuyuki Miyoshi, Isao Date

    Neurologia medico-chirurgica   51 ( 9 )   664 - 6   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 78-year-old man presented with a rare massive subarachnoid hematoma (SAH) in the cervical spine after coronary stenting for angina pectoris. Chest pain and electrocardiographic changes were resolved after administration of coronary dilator and coronary stenting, but shoulder pain persisted. At 6 hours after stenting, left hemiparesis was found with deteriorated shoulder pain. Computed tomography and magnetic resonance imaging revealed massive SAH in the cervical spine. Emergent hematoma evacuation with laminoplasty was performed because of rapid progression of the hemiparesis and pain. The hemiparesis was ameliorated after surgery. Spinal hematoma should be considered in the differential diagnosis in patients receiving anti-platelet or anti-coagulant drugs with rapid progression of pain.

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  • [Mist irrigation system at drilling in spinal surgery].

    Takao Yasuhara, Yasuyuki Miyoshi, Isao Date

    No shinkei geka. Neurological surgery   38 ( 12 )   1103 - 7   2010年12月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    The "mist irrigation system" (MIS) is a new and effective method at drilling in spinal surgery. In this report, MIS is introduced with subsequent demonstration that visibility at drilling is better with MIS because of the reduction of smoke, blood and irrigation water. Additionally using a 5 mm-thick acryl plate, the time for perforation by drilling and temperature after drilling with MIS, drip-irrigation (DI) or no irrigation, were measured respectivily. Using the acryl plate significantly reduced drilling time and high temperature after perforation in the group without irrigation were recognized, compared to cases in the groups with MIS or DI. The results might indicate that the high temperature of the drill might melt the acryl plate immediately. As a conclusion, MIS might help surgeons to drill in the deep and narrow operative field. Additionally it might help to reduce the risks of heat injury to neuronal tissue by cooling efficiently.

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  • Peri-hemorrhagic degeneration accompanies stereotaxic collagenase-mediated cortical hemorrhage in mouse. 国際誌

    Tadashi Masuda, Mina Maki, Koichi Hara, Takao Yasuhara, Noriyuki Matsukawa, SeongJin Yu, Eunkyung Cate Bae, Naoki Tajiri, Sonia H Chheda, Marianna Aurora Solomita, Nathan Weinbren, Yuji Kaneko, Sergei A Kirov, David C Hess, Hideki Hida, Cesar V Borlongan

    Brain research   1355   228 - 39   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The cortex is a key brain region vulnerable to intracerebral hemorrhage (ICH) associated with stroke and head trauma. Animal models of ICH, via blood or collagenase infusion, have been developed most commonly to target the striatum. Here, we show that stereotaxic injection of collagenase type IV into two sites of the right cortex of adult C57BL6 mice produced hemorrhage to the cortex, subcortical white matter and hippocampus at day 1 post-injury, followed by cortical volume decrement by day 7. Reductions in MAP2- and NeuN-positive neurons were detected at day 1 and 7 post-injury in the core and peri-hemorrhagic cortex, respectively. Fluoro-Jade positive degenerating neurons were observed at day 1 in the peri-hemorrhagic area. An aberrant aggregation of GFAP-positive astrocytes and a significant reduction in RIP-positive oligodendroglial cells were detected at day 7 post-injury in the cortical area. In addition, a significant decrement in retrogradely Cholera Toxin Subunit B-labeled corticospinal neurons was recognized at day 14 post-injury in the ipsilateral cortex. Among the behavioral tests employed, the pole climb movement test robustly detected significant motor dysfunction at day 1, 3, and 7 post-injury that positively but inversely correlated with cortical volume at day 1 and 7 post-injury, respectively. The consistent observation of neuronal cell loss in the hemorrhagic core that subsequently extended to degeneration of neurons in the peri-hemorrhagic area, with accompanying motor abnormalities at least up to the subacute phase, advances this cortical hemorrhage model as a platform for examining the pathophysiology of and experimental treatments for ICH.

    DOI: 10.1016/j.brainres.2010.07.101

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  • Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: focusing on neuroprotective effects of stromal cell-derived factor-1alpha. 査読 国際誌

    Feifei Wang, Takao Yasuhara, Tetsuro Shingo, Masahiro Kameda, Naoki Tajiri, Wen Ji Yuan, Akihiko Kondo, Tomohito Kadota, Tanefumi Baba, Judith Thomas Tayra, Yoichiro Kikuchi, Yasuyuki Miyoshi, Isao Date

    BMC neuroscience   11   52 - 52   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1alpha (SDF-1alpha) is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1alpha were explored. 6-hydroxydopamine (6-OHDA, 20 microg) was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 x 107 cells, respectively) or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1alpha were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA) assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL) staining. RESULTS: Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH)-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc) compared to that of control rats. In the in vitro study, SDF-1alpha treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. CONCLUSIONS: Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1alpha. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

    DOI: 10.1186/1471-2202-11-52

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  • 岡山大学病院小児頭蓋顔面形成センターにおける頭蓋縫合早期癒合症骨モデル作成による手術シミュレーションの効果と手術成績

    小野 成紀, 安原 隆雄, 山田 潔, 木股 敬裕, 本城 正, 山城 隆, 伊達 勲

    小児の脳神経   35 ( 2 )   212 - 212   2010年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • Exercise exerts neuroprotective effects on Parkinson's disease model of rats. 国際誌

    Naoki Tajiri, Takao Yasuhara, Tetsuro Shingo, Akihiko Kondo, Wenji Yuan, Tomohito Kadota, Feifei Wang, Tanefumi Baba, Judith Thomas Tayra, Takamasa Morimoto, Meng Jing, Yoichiro Kikuchi, Satoshi Kuramoto, Takashi Agari, Yasuyuki Miyoshi, Hidemi Fujino, Futoshi Obata, Isao Takeda, Tomohisa Furuta, Isao Date

    Brain research   1310   200 - 7   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function.

    DOI: 10.1016/j.brainres.2009.10.075

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  • Infantile cervical intramedullary cavernous angioma manifesting as hematomyelia. Case report.

    Yasuyuki Miyoshi, Takao Yasuhara, Masako Omori, Isao Date

    Neurologia medico-chirurgica   50 ( 8 )   677 - 82   2010年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 2-month-old infant presented with a cervical intramedullary spinal cord cavernous angioma manifesting as left hemiparesis caused by hematomyelia. Osteoplastic laminotomy of the cervical spine was carried out with subsequent microsurgical excision of the intramedullary spinal cord cavernous angioma. Magnetic resonance imaging revealed no residual tumor. At 25 months after the surgery, she presented no neurological deficit without recurrence and cervical deformity. This case of infantile intramedullary spinal cord cavernous angioma presenting with cervical hematomyelia shows osteoplastic laminotomy of the cervical spine might be helpful to prevent consequent cervical deformity in pediatric cases.

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  • Notch-induced rat and human bone marrow stromal cell grafts reduce ischemic cell loss and ameliorate behavioral deficits in chronic stroke animals. 国際誌

    Takao Yasuhara, Noriyuki Matsukawa, Koichi Hara, Mina Maki, Mohammed M Ali, Seong Jin Yu, Eunkyung Bae, Guolong Yu, Lin Xu, Michael McGrogan, Krys Bankiewicz, Casey Case, Cesar V Borlongan

    Stem cells and development   18 ( 10 )   1501 - 14   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Gene transfection with Notch 1 intracellular domain and subsequent growth factor treatment stimulate neuron-like differentiation of bone marrow stromal cells (BMSCs). Here, we examined the potential of transplanting Notch-induced BMSCs to exert therapeutic effects in a rat model of chronic ischemic stroke. In experiment 1, Notch-induced rat BMSCs were intrastriatally transplanted in rats at 1 month after being subjected to transient occlusion of middle cerebral artery (MCAo). Compared to post-stroke/pretransplantation level, significant improvements in locomotor and neurological function were detected in stroke rats that received 100 k and 200 k BMSCs, but not in those that received 40 k BMSCs. Histological results revealed 9%-15% graft survival, which dose-dependently correlated with behavioral recovery. At 5 weeks post-transplantation, some grafted BMSCs were positive for the glial marker GFAP (about 5%), but only a few cells (2-5 cells per brain) were positive for the neuronal marker NeuN. However, at 12 weeks post-transplantation, where the number of GFAP-positive BMSCs was maintained (5%), there was a dramatic increase in NeuN-positive BMSCs (23%). In experiment 2, Notch-induced human BMSCs were intrastriatally transplanted in rats at 1 month following the same MCAo model. Improvements in both locomotor and neurological function were observed from day 7 to day 28 post-transplantation, with the high dose (180 k) displaying significantly better behavioral recovery than the low dose (90 k) or vehicle. There were no observable adverse behavioral effects during this study period that also involved chronic immunosuppression of all animals. Histological analyses revealed a modest 5%-7% graft survival, with few (<1%) cells expressing an intermediate MAP2 neuronal marker, but not glial or oligodendroglial markers. In addition, striatal peri-infarct cell loss was significantly reduced in transplanted stroke animals compared to vehicle-treated stroke animals. The present study demonstrates the potential of Notch-induced BMSC cell therapy for patients presenting with fixed ischemic stroke.

    DOI: 10.1089/scd.2009.0011

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  • Erythropoietin exerts anti-epileptic effects with the suppression of aberrant new cell formation in the dentate gyrus and upregulation of neuropeptide Y in seizure model of rats. 国際誌

    Akihiko Kondo, Tetsuro Shingo, Takao Yasuhara, Satoshi Kuramoto, Masahiro Kameda, Yoichiro Kikuchi, Toshihiro Matsui, Yasuyuki Miyoshi, Takashi Agari, Cesario V Borlongan, Isao Date

    Brain research   1296   127 - 36   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We explored the effects of exogenous and endogenous erythropoietin (EPO) in a seizure model of rat. Adult male Fischer 344 rats received continuous intraventricular infusion of EPO dissolved in saline containing 1mg/ml of rat serum albumin, anti-EPO antibody, saline containing 1mg/ml of rat serum albumin or combined EPO and neuropeptide Y (NPY) Y2-receptor antagonist. Animals were behaviorally evaluated for seizure development over 6h after kainic acid injection followed by immunohistochemical assays. Mortality rate, seizure severity, apoptotic cell death and abnormal cell proliferation in the hippocampus of EPO-treated epileptic rats were significantly attenuated, compared to control rats. Anti-EPO antibody in non-EPO-treated animals worsened seizures and CA1 neuronal cell death, while NPY Y2-receptor antagonist cancelled the therapeutic effects of exogenous EPO. Both exogenous and endogenous EPO might modulate seizure severity and protect the hippocampal neurons in epileptic rats, via novel mechanistic pathways involving blockade of epileptogenic cell formation coupled with NPY receptor modulation in the hippocampus.

    DOI: 10.1016/j.brainres.2009.08.025

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  • Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/Akt signaling pathway. 国際誌

    Tanefumi Baba, Masahiro Kameda, Takao Yasuhara, Takamasa Morimoto, Akihiko Kondo, Tetsuro Shingo, Naoki Tajiri, Feifei Wang, Yasuyuki Miyoshi, Cesario V Borlongan, Mitsunori Matsumae, Isao Date

    Stroke   40 ( 11 )   e598-605   2009年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND PURPOSE: Neuroprotective effects of electric stimulation have been recently shown in ischemic stroke, but the underlying mechanisms remain poorly understood. METHODS: Adult Wistar rats weighing 200 to 250 g received occlusion of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion, electrodes were implanted to rats on the right frontal epidural space. Electric stimulation, at preset current (0 to 200 microA) and frequency (0 to 50 Hz), was performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days and 1 week postmiddle cerebral artery and then immediately euthanized for protein and immunohistochemical assays. After demonstration of behavioral and histological benefits, subsequent experiments pursued the mechanistic hypothesis that electric stimulation exerted antiapoptotic effects through the phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was performed in the presence or absence of specific inhibitors of phosphoinositide 3-kinase (LY294002) in stroke rats. RESULTS: Cortical stimulation abrogated the ischemia-associated increase in apoptotic cells in the injured cortex by activating antiapoptotic cascades, which was reversed by the phosphoinositide 3-kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically. Furthermore, brain levels of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor) were upregulated, which coincided with enhanced angiogenesis and suppressed proliferation of inflammatory cells in the ischemic cortex. CONCLUSIONS: These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia.

    DOI: 10.1161/STROKEAHA.109.563627

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  • The combined therapy of intrahippocampal transplantation of adult neural stem cells and intraventricular erythropoietin-infusion ameliorates spontaneous recurrent seizures by suppression of abnormal mossy fiber sprouting. 査読 国際誌

    Meng Jing, Tetsuro Shingo, Takao Yasuhara, Akihiko Kondo, Takamasa Morimoto, Feifei Wang, Tanefumi Baba, Wen Ji Yuan, Naoki Tajiri, Takashi Uozumi, Mayu Murakami, Mariko Tanabe, Yasuyuki Miyoshi, Shiguang Zhao, Isao Date

    Brain research   1295   203 - 17   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Adult neural stem cells (NSCs) possess the potentials to self-renew and exert neuroprotection. In this study, we examined whether adult NSCs had anti-epileptic effects in rats with status epilepticus (SE) induced by kainic acid (KA) and whether co-administration of erythropoietin (EPO) enhanced anti-epileptic effects or cell survival. Adult NSCs were transplanted into KA-lesioned hippocampus with or without intracerebroventricular EPO infusion. Electronic encephalography (EEG) was recorded for 3 weeks after transplantation. The frequency of abnormal spikes in rats with NSC transplantation decreased significantly compared to those of rats without NSC transplantation. Most of the transplanted NSCs differentiated into GFAP-positive astrocytes. EPO infusion significantly enhanced the survival of NSCs, but not neuronal differentiation or migration. NSC transplantation increased the number of neuropeptide Y (NPY) and glutamic acid decarboxylase 67 (GAD67)-positive interneurons. NSC transplantation also suppressed mossy fiber sprouting into the inner molecular layer with subsequent reduction of hippocampal excitability, which finally prevented the development of spontaneous recurrent seizures in adult rats after KA-induced SE. This study might shed light on the cytoarchitectural mechanisms of temporal lobe epilepsy as well as clarify the effect of adult NSC transplantation with intracerebroventricular EPO infusion for temporal lobe epilepsy.

    DOI: 10.1016/j.brainres.2009.07.079

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  • Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke. 国際誌

    Noriyuki Matsukawa, Takao Yasuhara, Koichi Hara, Lin Xu, Mina Maki, Guolong Yu, Yuji Kaneko, Kosei Ojika, David C Hess, Cesar V Borlongan

    BMC neuroscience   10   126 - 126   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. RESULTS: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. CONCLUSION: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.

    DOI: 10.1186/1471-2202-10-126

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  • Anomaly in aortic arch alters pathological outcome of transient global ischemia in Rhesus macaques. 国際誌

    Koichi Hara, Takao Yasuhara, Mina Maki, Noriyuki Matsukawa, Guolong Yu, Lin Xu, Laura Tambrallo, Nancy A Rodriguez, David M Stern, Tetsumori Yamashima, Jerry J Buccafusco, Takeshi Kawase, David C Hess, Cesario V Borlongan

    Brain research   1286   185 - 91   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We investigated a non-human primate (NHP) transient global ischemia (TGI) model which was induced by clipping the arteries originating from the aortic arch. Previously we demonstrated that our TGI model in adult Rhesus macaques (Macaca mulatta) results in marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. However, we observed varying degrees of hippocampal cell loss among animals. Here, we report for the first time an anomaly of the aortic arch in some Rhesus macaques that appears as a key surgical factor in ensuring the success of the TGI model in this particular NHP. Eleven adult Rhesus macaques underwent the TGI surgery, which involved 10-15-minute clipping of both innominate and subclavian arteries. Animals were allowed to survive between 1 day and 28 days after TGI. Because of our experience and knowledge that Japanese macaques exhibited only innominate and subclavian arteries arising from the aortic arch, macroscopic visualization of these two arteries alone in the Rhesus macaques initially assured us that clipping both arteries was sufficient to produce TGI. During the course of one TGI operation, however, we detected 3 arterial branches arising from the aortic arch, which prompted us to subsequently search for 3 branches in succeeding TGI surgeries. In addition, we performed post-mortem examination of the heart to confirm the number of arterial branches in the aortic arch. Finally, in order to reveal the pathological effect of the aortic arch anomaly, we compared the hippocampal cell loss between animals found to have 3 arterial branches but had all or only two branches clipped during TGI operation. Post-mortem examination revealed that eight NHPs had the typical two arterial aortic branches, but three NHPs displayed an extra arterial aortic branch, indicating that about 30% of Rhesus macaques had 3 arterial branches arising from the aorta. Histological analyses using Nissl staining showed that in NHPs with the aortic arch anomaly clipping only two of three arterial branches led to a partial cell loss and minimal alteration in number of cell layers in the hippocampal region when compared with clipping all three branches, with the hippocampal cell death in the latter resembling the pathological outcome achieved by clipping the two arterial branches in NHPs displaying the typical two-artery aortic arch. The finding that 3 of 11 NHPs exhibited an extra arterial aortic branch recognizes this aortic arch anomaly in Rhesus macaques that warrants a critical surgical maneuver in order to successfully produce consistent TGI-induced hippocampal cell loss.

    DOI: 10.1016/j.brainres.2009.06.015

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  • Injection of muscimol, a GABAa agonist into the anterior thalamic nucleus, suppresses hippocampal neurogenesis in amygdala-kindled rats. 国際誌

    Satoshi Kuramoto, Takao Yasuhara, Takashi Agari, Akihiko Kondo, Toshihiro Matsui, Yasuyuki Miyoshi, Tetsuro Shingo, Isao Date

    Neurological research   31 ( 4 )   407 - 13   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The relationship between neurogenesis and epilepsy remains to be solved so far, although aberrant electric circuit recognized in epilepsy might be involved in neurogenesis. In this study, neurogenesis and the proliferation of astrocytes in the subgranular zone of the hippocampus were explored using unilateral amygdala-kindled rats with or without muscimol, a gamma-aminobutyric acid a (GABAa) agonist injection into the bilateral anterior thalamic nuclei (AN). Muscimol injection significantly ameliorated the behavioral scores of epilepsy without any significant alteration on the electroencephalography recorded at the stimulated basolateral amygdala, thus suggesting that muscimol injection might affect the secondary generalization, but not the initial discharge itself. The number of bromodeoxyuridine (BrdU), BrdU/doublecortin and BrdU/glial fibrillary acidic protein-positive cells in the subgranular zone of kindled animals increased markedly. Muscimol injection significantly suppressed neurogenesis, but not the proliferation of astrocyte, in the subgranular zone of the non-stimulated side, probably through the suppression of secondary generalization via AN. The results might indicate the underlying relationships between neurogenesis and epilepsy, that epileptic propagation in unilateral amygdala-kindled rats might go through AN into the contralateral side with subsequent neurogenesis, although further studies need to clarify the hypothesis.

    DOI: 10.1179/174313208X346125

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  • Continuous intraventricular infusion of erythropoietin exerts neuroprotective/rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis. 査読 国際誌

    Tomohito Kadota, Tetsuro Shingo, Takao Yasuhara, Naoki Tajiri, Akihiko Kondo, Takamasa Morimoto, Wen Ji Yuan, Feifei Wang, Tanefumi Baba, Koji Tokunaga, Yasuyuki Miyoshi, Isao Date

    Brain research   1254   120 - 7   2009年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using L-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO treated rats significantly increased with migratory potencies to the damaged striatum,compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added.

    DOI: 10.1016/j.brainres.2008.11.094

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  • Neurological disorders and neural regeneration, with special reference to Parkinson's disease and cerebral ischemia.

    Isao Date, Takao Yasuhara

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   12 ( 1 )   11 - 6   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    For many years, it was recognized that brain and spinal cord tissues could not be regenerated once they were damaged. Recently, this concept has been challenged and many basic and clinical studies regarding neural regeneration and transplantation have been reported. In this review, we will summarize the clinical studies using cell transplantation for the treatment of Parkinson's disease and cerebral ischemia. Then, we will report the recent advancement of basic studies using cell lines and neural stem cells as donor tissue. Cell line grafting can be done by encapsulating desired cell line in semipermeable polymer hollow fibers, and neurotransmitter and neurotrophic factors can be delivered into the brain. Neural stem cells, especially those of adult origin, have the advantage that autologous cell transplantation can be done. The biological features of various types of stem cells have been widely investigated and will be applied to the treatment of neurological disorders through cell transplantation.

    DOI: 10.1007/s10047-008-0441-4

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  • Gene therapy for Parkinson's disease. 国際誌

    Takao Yasuhara, Isao Date

    Journal of neural transmission. Supplementum   ( 73 )   301 - 9   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Parkinson's disease is characterized by the degeneration of the nigrostriatal dopaminergic neurons with the manifestation of tremor, rigidity, akinesia, and disturbances of postural reflexes. Medication using L-DOPA and surgeries including deep brain stimulation are the established therapies for Parkinson's disease. Cell therapies are also effective and have rapidly developed with the recent advancement in molecular biological technology including gene transfer. In this review, ex vivo gene therapy using genetically engineered cell transplantation for Parkinson's disease model of animals is described, including catecholamine/neurotrophic factor-secreting cell transplantation with or without encapsulation, as well as in vivo gene therapy using direct injection of viral vector to increase dopamine-production, ameliorate the survival of dopaminergic neurons, correct the deteriorated microenvironment, or normalize genetic abnormality. Furthermore, the future directions for clinical application are described together with recent clinical trials of gene therapy.

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  • Intravenous grafts recapitulate the neurorestoration afforded by intracerebrally delivered multipotent adult progenitor cells in neonatal hypoxic-ischemic rats. 国際誌

    Takao Yasuhara, Koichi Hara, Mina Maki, Robert W Mays, Robert J Deans, David C Hess, James E Carroll, Cesar V Borlongan

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism   28 ( 11 )   1804 - 10   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Once hypoxic-ischemic (HI) injury ensues in the human neonate at birth, the resulting brain damage lasts throughout the individual's lifetime, as no ameliorative treatments are currently available. We have recently shown that intracerebral transplantation of multipotent adult progenitor cells (MAPCs) results in behavioral improvement and reduction in ischemic cell loss in neonatal rat HI-injury model. In an attempt to advance this cellular therapy to the clinic, we explored the more practical and less invasive intravenous administration of MAPCs. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, then 7 days later received intracerebral or intravenous injections of allogeneic rat MAPCs. On post-transplantation days 7 and 14, the animals that received MAPCs via the intracerebral or intravenous route exhibited improved motor and neurologic scores compared with those that received vehicle infusion alone. Immunohistochemical evaluations at day 14 after transplantation revealed that both intracerebrally and intravenously transplanted MAPCs were detected in the ischemic hippocampal area. The degree of hippocampal cell preservation was almost the same in the two treatment groups and greater than that in the vehicle group. These results show that intravenous delivery of MAPCs is a feasible and efficacious cell therapy with potential for clinical use.

    DOI: 10.1038/jcbfm.2008.68

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  • Embryonic neural stem cells transplanted in middle cerebral artery occlusion model of rats demonstrated potent therapeutic effects, compared to adult neural stem cells. 国際誌

    Kazuya Takahashi, Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Masahiro Kameda, Akira Takeuchi, Akimasa Yano, Kazuhiko Kurozumi, Takashi Agari, Yasuyuki Miyoshi, Kazushi Kinugasa, Isao Date

    Brain research   1234   172 - 82   2008年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cell therapy using stem cells is awaited by stroke patients with impaired movement and cognitive functions, although intravenous alteplase-administration ameliorated outcomes of patients receiving the therapy within 3 h of onset. In this study, we explored the therapeutic effects of neural progenitor cells (NPC) upon middle cerebral artery occlusion (MCAO) model of rats with exploration of the differences between adult and embryonic NPCs in therapeutic effects. GFP-labeled adult or embryonic NPCs were transplanted for transient MCAO model of rats at 1h after reperfusion. Rats were examined behaviorally using limb placement test, rotarod test and cylinder test with neuroradiological assessment using magnetic resonance imaging (MRI). Consequently after euthanasia, rats were immunohistochemically investigated to explore graft survival and immune reaction. MRI of rats receiving NPCs revealed significant reduction of infarct volumes, compared to vehicle-treated rats with corresponding behavioral amelioration. The transplanted cells were surviving in rats receiving NPCs, although the number of embryonic NPCs was significantly higher than that of adult NPCs. Iba-1-positive inflammatory cells of rats receiving adult NPCs were prominent, compared to those receiving embryonic NPCs, which might be a rationale for the differences between rats receiving adult and embryonic NPCs in the number of surviving NPCs. On the contraries, adult NPCs surely demonstrated therapeutic effects with a few surviving cells, thus indicating that the therapeutic effects might be due to trophic/growth factor-secretion from transplanted NPCs, rather than replacement of damaged host neurons. Therapeutic effects of NPCs for MCAO model of rats were clarified in this study. Transplantation of NPCs will be a hopeful strategy for stroke patients, although further studies are required for the patient safety and underlying mechanisms.

    DOI: 10.1016/j.brainres.2008.07.086

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  • Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons. 査読 国際誌

    Wen Ji Yuan, Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Takashi Agari, Masahiro Kameda, Takashi Uozumi, Naoki Tajiri, Takamasa Morimoto, Meng Jing, Tanefumi Baba, Feifei Wang, Hanbai Leung, Toshihiro Matsui, Yasuyuki Miyoshi, Isao Date

    BMC neuroscience   9   75 - 75   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of nigrostriatal dopaminergic systems. Free radicals induced by oxidative stress are involved in the mechanisms of cell death in PD. This study clarifies the neuroprotective effects of edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one), which has already been used for the treatment of cerebral ischemia in Japan, on TH-positive dopaminergic neurons using PD model both in vitro and in vivo. 6-hydroxydopamine (6-OHDA), a neurotoxin for dopaminergic neurons, was added to cultured dopaminergic neurons derived from murine embryonal ventral mesencephalon with subsequet administration of edaravone or saline. The number of surviving TH-positive neurons and the degree of cell damage induced by free radicals were analyzed. In parallel, edaravone or saline was intravenously administered for PD model of rats receiving intrastriatal 6-OHDA lesion with subsequent behavioral and histological analyses. RESULTS: In vitro study showed that edaravone significantly ameliorated the survival of TH-positive neurons in a dose-responsive manner. The number of apoptotic cells and HEt-positive cells significantly decreased, thus indicating that the neuroprotective effects of edaravone might be mediated by anti-apoptotic effects through the suppression of free radicals by edaravone. In vivo study demonstrated that edaravone-administration at 30 minutes after 6-OHDA lesion reduced the number of amphetamine-induced rotations significantly than edaravone-administration at 24 hours. Tyrosine hydroxylase (TH) staining of the striatum and substantia nigra pars compacta revealed that edaravone might exert neuroprotective effects on nigrostriatal dopaminergic systems. The neuroprotective effects were prominent when edaravone was administered early and in high concentration. TUNEL, HEt and Iba-1 staining in vivo might demonstrate the involvement of anti-apoptotic, anti-oxidative and anti-inflammatory effects of edaravone-administration. CONCLUSION: Edaravone exerts neuroprotective effects on PD model both in vitro and in vivo. The underlying mechanisms might be involved in the anti-apoptotic effects, anti-oxidative effects, and/or anti-inflammatory effects of edaravone. Edaravone might be a hopeful therapeutic option for PD, although the high therapeutic dosage remains to be solved for the clinical application.

    DOI: 10.1186/1471-2202-9-75

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  • Neural progenitor NT2N cell lines from teratocarcinoma for transplantation therapy in stroke. 国際誌

    Koichi Hara, Takao Yasuhara, Mina Maki, Noriyuki Matsukawa, Tadashi Masuda, Seong Jin Yu, Mohammed Ali, Guolong Yu, Lin Xu, Seung U Kim, David C Hess, Cesar V Borlongan

    Progress in neurobiology   85 ( 3 )   318 - 34   2008年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This review article discusses recent progress on the use of teratocarcinoma-derived Ntera2/D1 neuron-like cells (NT2N cells, also called hNT cells) as graft source for cell transplantation in stroke. Laboratory evidence has demonstrated the therapeutic potential of NT2N cells in stroke therapy. Phase I and II clinical trials have shown the cells' feasibility, safety and tolerability profiles in stroke patients. Despite these novel features of NT2N cells, the transplantation regimen remains to be optimized. Moreover, determining the mechanisms underlying the grafts' beneficial effects, specifically demonstrating functional synaptic connections between host brain and NT2N cell grafts, warrants further examination. The major limiting factor for initiating a large clinical trial is the cells' highly potent proliferative property due to their cancerous origin, thereby raising the concern that these cells may revert to a neoplastic state over time after transplantation. To this end, we explored a proof-of-concept "retroviral" strategy to further establish the post-mitotic status of NT2N cells by transfecting these cells with the transcription factor Nurr1, in addition to the standard treatment with retinoic acid and mitotic inhibitors. This new cell line NT2N.Nurr1 displays an expedited neuronal commitment and secretes a high level of the neurotrophic factor glial cell line-derived neurotrophic factor (GDNF), and when transplanted into the rodent stroke brain expressed neuronal phenotype and reduced behavioral impairments which are comparable, if not more robust, than those produced by NT2N cells. Such highly potent neuronal lineage commitment and neurotrophic factor secretory function of NT2.Nurr1 cells make them an appealing graft source for transplantation therapy.

    DOI: 10.1016/j.pneurobio.2008.04.005

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  • Intrapallidal metabotropic glutamate receptor activation in a rat model of Parkinson's disease: behavioral and histological analyses. 国際誌

    Takashi Agari, Takao Yasuhara, Toshihiro Matsui, Satoshi Kuramoto, Akihiko Kondo, Yasuyuki Miyoshi, Tetsuro Shingo, Cesario V Borlongan, Isao Date

    Brain research   1203   189 - 96   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.

    DOI: 10.1016/j.brainres.2008.01.051

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  • Dietary supplementation exerts neuroprotective effects in ischemic stroke model. 国際誌

    Takao Yasuhara, Koichi Hara, Mina Maki, Tadashi Masuda, Cyndy D Sanberg, Paul R Sanberg, Paula C Bickford, Cesar V Borlongan

    Rejuvenation research   11 ( 1 )   201 - 14   2008年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential.

    DOI: 10.1089/rej.2007.0608

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  • Comparison of the therapeutic potential of adult and embryonic neural precursor cells in a rat model of Parkinson disease. 国際誌

    Kenichiro Muraoka, Tetsuro Shingo, Takao Yasuhara, Masahiro Kameda, Wen Ji Yuen, Takashi Uozumi, Toshihiro Matsui, Yasuyuki Miyoshi, Isao Date

    Journal of neurosurgery   108 ( 1 )   149 - 59   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The therapeutic effects of adult and embryonic neural precursor cells (NPCs) were evaluated and their therapeutic potential compared in a rat model of Parkinson disease. METHODS: Adult NPCs were obtained from the subventricular zone and embryonic NPCs were taken from the ganglionic eminence of 14-day-old embryos. Each NPC type was cultured with epidermal growth factor. The in vitro neuronal differentiation rate of adult NPCs was approximately equivalent to that of embryonic NPCs after two passages. Next, the NPCs were transfected with either green fluorescent protein or glial cell line-derived neurotrophic factor (GDNF) by adenoviral infection and transplanted into the striata in a rat model of Parkinson disease (PD) induced by unilateral intrastriatal injection of 6-hydroxydopamine. An amphetamine-induced rotation test was used to evaluate rat behavioral improvement, and immunohistochemical analysis was performed to compare grafted cell survival, differentiation, and host tissue changes. RESULTS: The rats with GDNF-transfected NPCs had significantly fewer amphetamine-induced rotations and less histological damage. Except for the proportion of surviving grafted cells, there were no significant differences between adult and embryonic NPCs. CONCLUSIONS: Adult and embryonic NPCs have a comparable therapeutic potential in a rat model of PD.

    DOI: 10.3171/JNS/2008/108/01/0149

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  • Nanotechnology as an adjunct tool for transplanting engineered cells and tissues. 国際誌

    Cesar V Borlongan, Tadashi Masuda, Tiffany A Walker, Mina Maki, Koichi Hara, Takao Yasuhara, Noriyuki Matsukawa, Dwaine F Emerich

    Current molecular medicine   7 ( 7 )   609 - 18   2007年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, including the availability of a universal cell source that can be differentiated into specific cellular phenotypes, methods to protect the transplanted allogeneic or xenogeneic cells from rejection by the host immune system, techniques to enhance cellular integration of the transplant within the host tissue, strategies for in vivo detection and monitoring of the cellular implants, and new techniques to deliver genes to cells without eliciting a host immune response. Finding ways to circumvent these obstacles will benefit considerably from being able to understand, visualize, and control cellular interactions at a sub-micron level. Cutting-edge discoveries in the multidisciplinary field of nanotechnology have provided us a platform to manipulate materials, tissues, cells, and DNA at the level of and within the individual cell. Clearly, the scientific innovations achieved with nanotechnology are a welcome strategy for enhancing the generally encouraging results already achieved in cell transplantation. This review article discusses recent progress in the field of nanotechnology as a tool for tissue engineering, gene therapy, cell immunoisolation, and cell imaging, highlighting its direct applications in cell transplantation therapy.

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  • Hippocampal CA1 cell loss in a non-human primate model of transient global ischemia: a pilot study. 国際誌

    Koichi Hara, Takao Yasuhara, Noriyuki Matsukawa, Mina Maki, Tadashi Masuda, Guolong Yu, Lin Xu, Laura Tambrallo, Nancy A Rodriguez, David M Stern, Takeshi Kawase, Tetsumori Yamashima, Jerry J Buccafusco, David C Hess, Cesario V Borlongan

    Brain research bulletin   74 ( 1-3 )   164 - 71   2007年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We exposed adult Rhesus (Macaca mulatta) to a transient global ischemia, which was induced by clipping the innominate and subclavian arteries that originated from the aortic arch. NHP1 received 20-min, while NHP2 and NHP3, were exposed to a 15-min transient global ischemia and were euthanized at day 1 (NHP1), day 5 (NHP2) or day 30 (NHP3) after ischemia, respectively. NHP1 displayed severe paralysis and rigidity, and intermittent convulsions over the next 24 h. Although histological examination of the brain revealed no detectable gross brain damage (i.e., swelling) and only minimal cell loss in the hippocampus, the acute survival time after surgery likely prevented the cerebral ischemia to fully develop and to be morphologically manifested. Nonetheless, the 20-min ischemia might have been too severe and caused a systemic multiple organ collapse that produced the abnormal behavioral symptoms. On the other hand, NHP2 and NHP3 which received 15-min ischemia only exhibited minor hindlimb paralysis. Indeed, by 48 h after ischemia, both animals appeared fully recovered with only fine motor deficits. Immunohistochemical examination revealed that NHP2 and 3, but not NHP1, had a marked neuronal cell loss in the hippocampal region, specifically the cornu Ammonis (CA1) region. The cell loss in these two ischemic NHP hippocampi was further confirmed by direct comparison with a normal Rhesus brain. These findings replicate the brain pathology seen in Japanese macaques exposed to the same ischemia model [T. Tsukada, M. Watanabe, T. Yamashima, Implications of CAD and DNase II in ischemic neuronal necrosis specific for the primate hippocampus, J. Neurochem. 79 (2001) 1196-1206; T. Yamashima, Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates, Prog. Neurobiol. 62 (2000) 273-295; T. Yamashima, Y. Kohda, K. Tsuchiya, T. Ueno, J. Yamashita, T. Yoshioka, E. Kominami, Inhibition of ischemic hippocampal neuronal death in primates with cathepsin B inhibitor CA-074: a novel strategy for neuroprotection based on calpain-cathepsin hypothesis, Eur. J. Neurosci. 10 (1998) 1723-1733; T. Yamashima, T.C. Saido, M. Takita, A. Miyazawa, J. Yamano, A. Miyakawa, H. Nishijyo, J. Yamashita, S. Kawashima, T. Ono, T. Yoshioka, Transient brain ischemia provokes Ca2+, PIP2 and calpain responses prior to delayed neuronal death in monkeys, Eur. J. Neurosci. 8 (1996) 1932-1944; T. Yamashima, A.B. Tonchey, T. Tsukada, T.C. Saido, S. Imajoh-Ohmi, T. Momoi, E. Kominami, Sustained calpain activation associated with lysosomal rupture executes necrosis of the postischemic CA1 neurons in primates, Hippocampus 13 (2003) 791-800]. The present minimally invasive transient global ischemia model using Rhesus shows many histopathological symptoms seen in human patients who experienced global ischemia, and should allow translational validation of experimental therapeutics for ischemic injury. Additional studies are warranted to reveal behavioral deficits associated with this ischemia model.

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  • [Autologous transplantation of adult derived neural stem cells].

    Tetsuro Shingo, Takao Yasuhara, Kenichiro Muraoka, Masahiro Kameda, Isao Date

    No shinkei geka. Neurological surgery   35 ( 8 )   823 - 9   2007年8月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Transplantation of post-mitotic human neuroteratocarcinoma-overexpressing Nurr1 cells provides therapeutic benefits in experimental stroke: in vitro evidence of expedited neuronal differentiation and GDNF secretion. 国際誌

    Koichi Hara, Noriyuki Matsukawa, Takao Yasuhara, Lin Xu, Guolong Yu, Mina Maki, Takeshi Kawase, David C Hess, Seung U Kim, Cesar V Borlongan

    Journal of neuroscience research   85 ( 6 )   1240 - 51   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Nurr1 has been implicated as a transcription factor mediating the endogenous neuroprotective mechanism against stroke. We examined the in vivo and in vitro properties of a new human embryonic carcinoma Ntera-2 cell line carrying the human Nurr1 gene (NT2N.Nurr1). Adult Sprague-Dawley rats underwent experimental stroke initially and 14 days later were assigned randomly to receive stereotaxic transplantation of NT2N.Nurr1 cells or infusion of vehicle into their ischemic striatum. Transplantation of NT2N.Nurr1 cells promoted significant attenuation of behavioral impairments over a 56-day period after stroke, characterized by decreased hyperactivity, biased swing activity, and neurologic deficits, as well as significant reduction in ischemic striatal cell loss compared to vehicle-infused stroke animals. Transplanted NT2N.Nurr1 cells survived and expressed neuronal phenotypic markers in the ischemic striatum. In vitro results showed that cultured NT2.Nurr1 cells were already negative for nestin even before retinoic acid treatment, despite strong nestin immunoreactivity in NT2 cells. This indicates Nurr1 triggered a rapid commitment of NT2 cells into a neuronal lineage. Indeed, NT2.Nurr1 cells, at 4 weeks into RA treatment, displayed more abundant tyrosine hydroxylase positive cells than NT2 cells. Parallel ELISA studies showed further that cultured NT2N.Nurr1, but not NT2N cells, secreted glial cell derived neurotrophic factor. The present study shows efficacy of NT2N.Nurr1 cell grafts in ischemic stroke, with in vitro evidence suggesting the cells' excellent neuronal differentiation capability and ability to secrete GDNF as likely mechanisms mediating the observed therapeutic benefits.

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  • Glial cell line-derived neurotrophic factor (GDNF) therapy for Parkinson's disease.

    Takao Yasuhara, Tetsuro Shingo, Isao Date

    Acta medica Okayama   61 ( 2 )   51 - 6   2007年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Many studies using animals clarify that glial cell line-derived neurotrophic factor (GDNF) has strong neuroprotective and neurorestorative effects on dopaminergic neurons. Several pilot studies clarified the validity of continuous intraputaminal GDNF infusion to patients with Parkinson's disease (PD), although a randomized controlled trial of GDNF therapy published in 2006 resulted in negative outcomes, and controversy remains about the efficacy and safety of the treatment. For a decade, our laboratory has investigated the efficacy and the most appropriate method of GDNF administration using animals, and consequently we have obtained some solid data that correspond to the results of clinical trials. In this review, we present an outline of our studies and other key studies related to GDNF, the current state of the research, problems to be overcome, and predictions regarding the use of GDNF therapy for PD in the future.

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  • Increased 8-OHdG levels in the urine, serum, and substantia nigra of hemiparkinsonian rats. 国際誌

    Takao Yasuhara, Koichi Hara, Kapil D Sethi, John C Morgan, Cesario V Borlongan

    Brain research   1133 ( 1 )   49 - 52   2007年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    8-Hydroxy-2'-deoxyguanosine (8-OHdG), the predominant marker of oxidative DNA damage, may be a good biomarker for monitoring the progression of Parkinson's disease (PD). Unfortunately, there are no basic laboratory data examining 8-OHdG levels in animal models of PD. In this study, we demonstrate that rats lesioned with 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle display significantly elevated 8-OHdG levels in urine, serum, and substantia nigra, but not cerebrospinal fluid and striatum, compared to sham controls. These increments in 8-OHdG levels were detected at 2 days, but not at 7 days after the lesion suggesting that oxidative stress is restricted to the acute phase of 6-OHDA neurotoxicity. The present results support 8-OHdG as a biomarker that may aid both in the diagnosis and in the documentation of progression in PD.

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  • Intracerebral transplantation of genetically engineered cells for Parkinson's disease: toward clinical application. 国際誌

    Takao Yasuhara, Isao Date

    Cell transplantation   16 ( 2 )   125 - 32   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Over the last decade, molecular biology has progressively developed, leading to new technology with subsequent clinical application for various cerebral diseases including Parkinson's disease (PD), one of the most investigated neurodegenerative disorders. The therapy for PD is mainly composed of medication, including drug replacement therapy, surgical treatment, and cell transplantation. Cell therapy for PD has been explored by using fetal nigral cells as an allo- or xenograft, autologous sympathetic ganglion, adrenal medulla, and carotid body in clinical settings. In addition, neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF), have a strong potency to rescue degenerating dopaminergic cells. Protein and/or gene therapy also might be a therapeutic option for PD. In this review, genetically engineered cell transplantation for animal models of PD, including catecholamine/neurotrophic factor-secreting cell transplantation with or without encapsulation, as performed in our laboratories, and their potential future as clinical applications are described with recent clinical studies in this field.

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  • Transplantation of bone marrow-derived stem cells: a promising therapy for stroke. 国際誌

    Yamei Tang, Takao Yasuhara, Koichi Hara, Noriyuki Matsukawa, Mina Maki, Guolong Yu, Lin Xu, David C Hess, Cesario V Borlongan

    Cell transplantation   16 ( 2 )   159 - 69   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Stroke remains a major cause of death in the US and around the world. Over the last decade, stem cell therapy has been introduced as an experimental treatment for stroke. Transplantation of stem cells or progenitors into the injured site to replace the nonfunctional cells, and enhancement of proliferation or differentiation of endogenous stem or progenitor cells stand as the two major cell-based strategies. Potential sources of stem/progenitor cells for stroke include fetal neural stem cells, embryonic stem cells, neuroteratocarcinoma cells, umbilical cord blood-derived nonhematopoietic stem cells, and bone marrow-derived stem cells. The goal of this article is to provide an update on the preclinical use of bone marrow-derived stem cells with major emphasis on mesenchymal stem cells (MSCs) and multipotent adult progenitor cells (MAPCs) because they are currently most widely applied in experimental stroke studies and are now being phased into early clinical trials. The phenotypic features of MSCs and MAPCs, as well as their application in stroke, are described.

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  • Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease. 国際誌

    Takao Yasuhara, Noriyuki Matsukawa, Koichi Hara, Guolong Yu, Lin Xu, Mina Maki, Seung U Kim, Cesario V Borlongan

    The Journal of neuroscience : the official journal of the Society for Neuroscience   26 ( 48 )   12497 - 511   2006年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neural stem cells (NSCs) possess high potencies of self-renewal and neuronal differentiation. We explored here whether transplantation of human NSCs cloned by v-myc gene transfer, HB1.F3 cells, is a feasible therapeutic option for Parkinson's disease. In vivo, green fluorescent protein-labeled HB1.F3 cells (200,000 viable cells in 3 microl of PBS) when stereotaxically transplanted (same-day lesion-transplant paradigm) into the 6-hydroxydopamine-lesioned striatum of rats significantly ameliorated parkinsonian behavioral symptoms compared with controls (vehicle, single bolus, or continuous minipump infusion of trophic factor, or killed cell grafts). Such graft-derived functional effects were accompanied by preservation of tyrosine hydroxylase (TH) immunoreactivity along the nigrostriatal pathway. Grafted HB1.F3 cells survived in the lesioned brain with some labeled with neuronal marker mitogen-activated protein 2 and decorated with synaptophysin-positive terminals. Furthermore, endogenous neurogenesis was activated in the subventricular zone of transplanted rats. To further explore the neuroprotective mechanisms underlying HB1.F3 cell transplantation, we performed cell culture studies and found that a modest number of HB1.F3 cells were TH and dopamine and cAMP-regulated phosphoprotein 32 positive, although most cells were nestin positive, suggesting a mixed population of mature and immature cells. Administration of the HB1.F3 supernatant to human derived dopaminergic SH-SY5Y cells and fetal rat ventral mesencephalic dopaminergic neurons protected against 6-hydroxydopamine neurotoxicity by suppressing apoptosis through Bcl-2 upregulation, which was blocked by anti-stem cell factor antibody alone, the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one] alone, or a combination of both. These results suggest that HB1.F3 cell transplantation exerts neuroprotective effects against dopaminergic depletion in vitro and in vivo because of trophic factor secretion and neuronal differentiation.

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  • Control of dopamine-secretion by Tet-Off system in an in vivo model of parkinsonian rat. 国際誌

    Kazuki Kobayashi, Takao Yasuhara, Takashi Agari, Kenichiro Muraoka, Masahiro Kameda, Wen Ji Yuan, Hitoshi Hayase, Toshihiro Matsui, Yasuyuki Miyoshi, Tetsuro Shingo, Isao Date

    Brain research   1102 ( 1 )   1 - 11   2006年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We established a PC12 cell line (PC12TH Tet-Off) in which human tyrosine hydroxylase (TH) expression can be negatively controlled by Doxycycline (Dox). First, dopamine (DA)-secretion from PC12TH Tet-Off cells was controlled by Dox-administration in a dose-responsive manner ranging from 0 to 100 ng/ml for 70 days in vitro. Furthermore, Parkinson's disease model of rats receiving encapsulated PC12TH Tet-Off cells displayed a significant decrease of dopamine concentration in the cerebrospinal fluid (CSF) and increase of the number of apomorphine-induced rotations by Dox-administration, as compared to transplanted rats without Dox-administration, although the significant decrease of the reduction ratio of DA concentration in the CSF with Dox-administration was recognized over time. At 2 months post-implantation, concentration of dopamine in the implanted striatum and from the retrieved capsules demonstrated that the control of DA-secretion could be partially achieved for 2 months in vivo. Our results support both the value of cell therapy using Tet-Off system and the technique of encapsulation might be a feasible option for Parkinson's disease especially in resolving the problem of dopamine oversupply in the future, although a more efficient way to control DA-secretion with quicker regulation and much titration of dose should be explored before clinical application.

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  • Ex vivo gene therapy: transplantation of neurotrophic factor-secreting cells for cerebral ischemia. 国際誌

    Takao Yasuhara, Cesario V Borlongan, Isao Date

    Frontiers in bioscience : a journal and virtual library   11   760 - 75   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Expressions of various neurotrophic factors or their receptors fluctuate after stroke, which in part prompted investigations into the efficacy of neurotrophic factors as treatment modality for stroke. The methods to deliver neurotrophic factors into the brain can be categorized into: 1) the surgical route of administration, such as intracerebral, intraventricular, intra-arterial, or intravenous systemic administration and 2) the manipulation of the therapeutic molecules via ex vivo or in vivo techniques. With ex vivo method, genetically engineered cells, including the use of autologous cells, have been explored. In this review, the potent therapeutic applications of neurotrophic factors in stroke are described, with emphasis on ex vivo methods, especially transplantation of encapsulated stem cells modified with adenovirus. Neurotrophic factor delivery, combined with ex vivo method, poses as novel treatment for stroke, although additional safety and efficacy studies remain to be examined.

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  • Gene therapy, cell transplantation and stroke. 国際誌

    Cesario V Borlongan, Christina Fournier, Christine E Stahl, Guolong Yu, Lin Xu, Noriyuki Matsukawa, Mary Newman, Takao Yasuhara, Koichi Hara, David C Hess, Paul R Sanberg

    Frontiers in bioscience : a journal and virtual library   11   1090 - 101   2006年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The use of neuroteratocarcinoma cells for transplantation therapy in stroke has emerged as a strategy for cell replacement therapy that has begun its transition from basic science laboratories to a clinical setting. Procurement logistics and novel neuroprotective functions associated with these cells allow neuroteratocarcinoma cells to serve as efficacious alternatives to using fetal cells as donor cell grafts for stroke therapy, although the optimal transplantation regimen must still be determined. In particular, the limitations of current stroke treatments and management reveal an urgent need to examine the efficacy of experimental treatments, such as neural transplantation, in order to develop better treatment therapies. This chapter will discuss the characteristics of NT2N cells, the role of the host brain microenvironment and NT2N cell grafts, laboratory research and clinical trials for the intracerebral transplantation of NT2N cells in stroke, the mechanisms underlying the grafts' effects, and NT2N cell grafts and the need for immunosuppression. This chapter will also highlight some of the most recent findings regarding NT2N cells.

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  • Transplantation of cryopreserved human bone marrow-derived multipotent adult progenitor cells for neonatal hypoxic-ischemic injury: targeting the hippocampus. 国際誌

    Takao Yasuhara, Noriyuki Matsukawa, Guolong Yu, Lin Xu, Robert W Mays, Jim Kovach, Robert Deans, David C Hess, James E Carroll, Cesar V Borlongan

    Reviews in the neurosciences   17 ( 1-2 )   215 - 25   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    There is currently no treatment for neonatal hypoxic-ischemic (HI) injury. Although limited clinical trials of stem cell therapy have been initiated in a number of neurological disorders, the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. Stem cell therapy, via stimulation of endogenous stem cells or transplantation of exogenous stem cells, has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has also been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents a highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. In the present study, we investigated the efficacy of intrahippocampal transplantation of multipotent adult progenitor cells (MAPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day old Sprague-Dawley rats were initially subjected to unilateral HI injury, that involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI

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  • Behavioral and histological characterization of intrahippocampal grafts of human bone marrow-derived multipotent progenitor cells in neonatal rats with hypoxic-ischemic injury. 国際誌

    Takao Yasuhara, Noriyuki Matsukawa, Guolong Yu, Lin Xu, Robert W Mays, Jim Kovach, Robert J Deans, David C Hess, James E Carroll, Cesar V Borlongan

    Cell transplantation   15 ( 3 )   231 - 8   2006年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Children born with hypoxic-ischemic (HI) brain injury account for a significant number of live births wherein no clinical treatment is available. Limited clinical trials of stem cell therapy have been initiated in a number-of neurological disorders, but the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. One major postulated mechanism underlying therapeutic benefits of stem cell therapy involves stimulation of endogenous neurogenesis via transplantation of exogenous stem cells. To this end, transplantation has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents as highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. Here, we investigated the efficacy of intrahippocampal transplantation of multipotent progenitor cells (MPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, which involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI injury, animals received stereotaxic hippocampal injections of vehicle or cryopre-served MPCs (thawed just prior to transplantation) derived either from Sprague-Dawley rats (syngeneic) or Fisher rats (allogeneic). All animals were treated with daily immunosuppression throughout the survival period. Behavioral tests were conducted on posttransplantation days 7 and 14 using the elevated body swing test and the rotarod to reveal general and coordinated motor functions. MPC transplanted animals exhibited reduced motor asymmetry and longer time spent on the rotarod than those that received the vehicle infusion. Both syngeneic and allogeneic MPC transplanted injured animals did not significantly differ in their behavioral improvements at both test periods. Immunohistochemical evaluations of graft survival after behavioral testing at day 14 posttransplantation revealed that syngeneic and allogeneic transplanted MPCs survived in the hippocampal region. These results demonstrate for the first time that transplantation of MPCs ameliorated motor deficits associated with HI injury. In view of comparable behavioral recovery produced by syngeneic and allogeneic MPC grafts, allogeneic transplantation poses as a feasible and efficacious cell replacement strategy with direct clinical application. An equally major finding is the observation lending support to the hippocampus as an excellent target brain region for stem cell therapy in treating HI injury.

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  • Article Commentary: Cell Transplantation: Stem Cells in the Spotlight. 国際誌

    Cesar V Borlongan, Guolong Yu, Noriyuki Matsukawa, Takao Yasuhara, Koichi Hara, Lin Xu

    Cell transplantation   14 ( 8 )   519 - 526   2005年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3727/000000005783982774

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  • Neurorescue effects of VEGF on a rat model of Parkinson's disease. 国際誌

    Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Masahiro Kameda, Takashi Agari, Yuan Wen Ji, Hitoshi Hayase, Hirofumi Hamada, Cesario V Borlongan, Isao Date

    Brain research   1053 ( 1-2 )   10 - 8   2005年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascular endothelial growth factor (VEGF) has been shown to display neuroprotective effects on dopaminergic (DA) neurons. Here, we investigated the neurorescue effects of VEGF on 6-hydroxydopamine (6-OHDA)-treated DA neurons in vitro and in vivo. Initially, we examined in vitro whether 1, 10, or 100 ng/ml of VEGF administration at 2 or 4 h after 6-OHDA treatment rescued DA neurons derived from E14 murine ventral mesencephalon. The earlier treatment of VEGF suppressed 6-OHDA-induced loss of DA neurons more than the delayed treatment. Next, we examined whether the continuous infusion of VEGF had neurorescue effects in a rat model of Parkinson's disease. We established a human VEGF secreting cell line (BHK-VEGF) and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally transplanted into the striatum of adult rats at 1 or 2 weeks after 6-OHDA lesions, and animals subsequently underwent behavioral and immunohistochemical evaluations. Compared to lesioned rats that received BHK-Control capsules, lesioned rats transplanted with BHK-VEGF capsules showed a significant reduction in the number of amphetamine-induced rotations, a significant preservation of TH-positive neurons in the substantia nigra pars compacta, and a remarkable glial proliferation in the striatum, with the earlier transplantation exerting much more benefits than the delayed transplantation. Parallel studies revealed that the observed in vitro and in vivo neurorescue effects were likely mediated by VEGF's angiogenic and glial proliferative effects, as well as its direct effects on the neurons. Our results suggest that VEGF is a highly potent neurorescue molecule for Parkinson's disease therapy.

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  • Encapsulated vascular endothelial growth factor-secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia. 国際誌

    Akimasa Yano, Tetsuro Shingo, Akira Takeuchi, Takao Yasuhara, Kazuki Kobayashi, Kazuya Takahashi, Kenichiro Muraoka, Toshihiro Matsui, Yasuyuki Miyoshi, Hirofumi Hamada, Isao Date

    Journal of neurosurgery   103 ( 1 )   104 - 14   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECT: The authors evaluated the neuroprotective and angiogenic effects of a continuous and low-dose infusion of vascular endothelial growth factor (VEGF)-165 on cerebral ischemia in rats. METHODS: The authors introduced VEGF complementary (c)DNA into baby hamster kidney (BHK) cells and established a cell line that produces human VEGF165 (BHK-VEGF). The BHK-VEGF cells and BHK cells that had been transfected with an expression vector that did not contain human VEGF165 cDNA (BHK-control) were encapsulated. Both capsules were implanted into rat striata. Six days after capsule implantation, the right middle cerebral artery (MCA) was occluded. Some animals were killed 24 hours after occlusion to measure the volume of the resulting infarct and to perform immunohistochemical studies. Other animals were used for subsequent behavioral studies 1, 7, and 14 days after MCA occlusion. The encapsulated BHK-VEGF cell grafts significantly reduced the volume of the infarct and the number of apoptotic cells in the penumbral area when compared with the effect of the BHK-control cell capsule. In addition, angiogenesis and gliogenesis significantly increased in the region around the capsule in animals that received BHK-VEGF cell capsules without an increase in focal cerebral blood flow; this did not occur in animals that received the BHK-control cell capsule. In behavioral studies rats that received the BHK-VEGF cell capsule displayed significant recovery while participating in the accelerating rotarod test after stroke. CONCLUSIONS: Continuous intracerebral administration of low-dose VEGF165 through encapsulated grafts of VEGF-producing cells produces neuroprotective and angiogenic effects. These effects improve subsequent motor function.

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  • Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats. 国際誌

    Shinji Katsuragi, Tomoaki Ikeda, Isao Date, Tetsuro Shingo, Takao Yasuhara, Kenichi Mishima, Naoya Aoo, Kazuhiko Harada, Nobuaki Egashira, Katsunori Iwasaki, Michihiro Fujiwara, Tsuyomu Ikenoue

    American journal of obstetrics and gynecology   192 ( 4 )   1028 - 37   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. STUDY DESIGN: Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. RESULTS: The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average number of correct choices was 6.2 +/- 0.1 versus 6.9 +/- 0.1 ( P < .01); in the choice reaction time test, average reaction time for a correct response was 2.35 +/- 0.1 seconds versus 1.97 +/- 0.09 seconds ( P < .01); in the water maze test, average swimming length was 1120.0 +/- 95.2 cm versus 841.6 +/- 92.1 cm ( P < .01). All results for the glial cell line-derived neurotrophic factor group were similar to those for the control group. CONCLUSION: Glial cell line-derived neurotrophic factor treatment is effective in not only reducing brain damage but also inhibiting learning and memory impairment, following hypoxic-ischemic insult in neonatal rats. No adverse effects in learning and memory tests were observed in the glial cell line-derived neurotrophic factor group.

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  • Grafting of glial cell line-derived neurotrophic factor secreting cells for hypoxic-ischemic encephalopathy in neonatal rats. 国際誌

    Shinji Katsuragi, Tomoaki Ikeda, Isao Date, Tetsuro Shingo, Takao Yasuhara, Tsuyomu Ikenoue

    American journal of obstetrics and gynecology   192 ( 4 )   1137 - 45   2005年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system. STUDY DESIGN: Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined. RESULTS: The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group. CONCLUSION: Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult.

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  • The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model. 国際誌

    Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Yuan wen Ji, Masahiro Kameda, Akira Takeuchi, Akimasa Yano, Shinsaku Nishio, Toshihiro Matsui, Yasuyuki Miyoshi, Hirofumi Hamada, Isao Date

    Brain research   1038 ( 1 )   1 - 10   2005年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects on dopaminergic (DA) neurons. In this study, we investigated whether the effects of VEGF were dose-dependent or not. First, VEGF was shown to be neuroprotective on 6-hydroxydopamine (6-OHDA)-treated murine DA neurons in vitro, although the 1 ng/ml of VEGF displayed more neuroprotective effects than 100 ng/ml. Furthermore, using 2 sizes of capsules (small/large) with different secreting quantities, 6-OHDA-treated rats receiving the small capsule filled with VEGF-secreting cells (BHK-VEGF) into the striatum showed a significant decrease in amphetamine-induced rotational behavior in number and a significant preservation of TH-positive fibers compared to those receiving the large BHK-VEGF capsule as well as those receiving BHK-Control capsule. Rats receiving the large BHK-VEGF capsule showed much more glial proliferation, angiogenesis, and brain edema around the capsule than those with the small one. High-dose administration of VEGF might cause poor circulation related to brain edema, although low-dose administration of VEGF displays neuroprotective effects on DA neurons. Our results demonstrate the importance of administration dose of VEGF, suggesting that low-dose administration of VEGF might be desirable for Parkinson's disease.

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  • Early transplantation of an encapsulated glial cell line-derived neurotrophic factor-producing cell demonstrating strong neuroprotective effects in a rat model of Parkinson disease. 国際誌

    Takao Yasuhara, Tetsuro Shingo, Kenichiro Muraoka, Kazuki Kobayashi, Akira Takeuchi, Akimasa Yano, Yuan Wenji, Masahiro Kameda, Toshihiro Matsui, Yasuyuki Miyoshi, Isao Date

    Journal of neurosurgery   102 ( 1 )   80 - 9   2005年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has been shown to confer neuroprotective effects on dopaminergic neurons. The authors investigated the effects of GDNF on 6-hydroxydopamine (6-OHDA)-treated dopaminergic neurons in vitro and in vivo. METHODS: First, the authors examined how 1, 10, or 100 ng/ml of GDNF, administered to cells 24 hours before, simultaneously with, or 2 or 4 hours after 6-OHDA was added, affected dopaminergic neurons. In a primary culture of E14 murine ventral mesencephalic neurons, earlier treatment with the higher dosage of GDNF suppressed 6-OHDA-induced loss of dopaminergic neurons better than later treatment. Next, the authors examined whether continuous infusion of GDNF at earlier time points would demonstrate a greater neuroprotective effect in a rat model of Parkinson disease (PD). They established a human GDNF-secreting cell line, called BHK-GDNF, and encapsulated the cells into hollow fibers. The encapsulated cells were unilaterally implanted into the striatum of adult rats 1 week before; simultaneously with; or 1, 2, or 4 weeks after 6-OHDA was given to induce lesions of the same striatum. With the earlier transplantation of a BHK-GDNF capsule, there was a significant reduction in the number of amphetamine-induced rotations displayed by the animals. Rats that had received earlier implantation of BHK-GDNF capsules displayed more tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta and a tendency for glial proliferation in the striatum. CONCLUSIONS: These neuroprotective effects may be related to glial proliferation and signaling via the GDNF receptor alpha1. The results of this study support a role for this grafting technique in the treatment of PD.

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  • Cell transplantation: stem cells in the spotlight. 国際誌

    Cesar V Borlongan, Guolong Yu, Noriyuki Matsukawa, Takao Yasuhara, Koichi Hara, Lin Xu

    Cell transplantation   14 ( 8 )   519 - 26   2005年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Pseudoxanthoma elasticum with carotid rete mirabile. 国際誌

    Takao Yasuhara, Kenji Sugiu, Mikio Kakishita, Isao Date

    Clinical neurology and neurosurgery   106 ( 2 )   114 - 7   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We describe a case of Pseudoxanthoma elasticum (PXE) in a 14-year-old girl. This case is especially rare because of its association with carotid rete mirabile (CRM). Only three cases have been reported previously in the literature. Although the relation between P. elasticum and carotid rete mirabile is unclear, both disorders are believed to be major risk factors for cerebrovascular disease.

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  • Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease. 国際誌

    Takao Yasuhara, Tetsuro Shingo, Kazuki Kobayashi, Akira Takeuchi, Akimasa Yano, Kenichiro Muraoka, Toshihiro Matsui, Yasuyuki Miyoshi, Hirofumi Hamada, Isao Date

    The European journal of neuroscience   19 ( 6 )   1494 - 504   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Vascular endothelial growth factor (VEGF) has previously been shown to display neuroprotective effects following ischemia, suggesting that VEGF may potentially be applied as a neuroprotective agent for the treatment of other neurological diseases. In this study, we investigated the neuroprotective capacity of VEGF in a model of Parkinson's disease. VEGF was found to be neuroprotective against cell death of primary E14 murine ventral mesencephalic neurons induced by 6-hydroxydopamine (6-OHDA) treatment in vitro. Further, rats receiving a continuous infusion of VEGF into the striatum via encapsulated hVEGF-secreting cells (baby hamster kidney-VEGF) displayed a significant decrease in amphetamine-induced rotational behavior and a significant preservation of tyrosine hydroxylase-positive neurons and fibers compared with control animals. VEGF likely functions via direct mechanisms by signaling through the neuropilin receptor expressed upon dopaminergic neurons in response to 6-OHDA treatment. Further, VEGF is likely to promote neuroprotection indirectly by activating the proliferation of glia and by promoting angiogenesis. Our results support a potential neuroprotective role for VEGF in the treatment of Parkinson's disease.

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  • The potential role of vascular endothelial growth factor in the central nervous system. 国際誌

    Takao Yasuhara, Tetsuro Shingo, Isao Date

    Reviews in the neurosciences   15 ( 4 )   293 - 307   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    During the past decade, vascular endothelial growth factor (VEGF) has been widely investigated, and reported to have pleiotropic functions in the central nervous system (CNS) and its supporting physiological environment. VEGF is involved in not only such well-known functions as angiogenesis, accentuation of vessel permeability, and glial proliferation, but also more recently acknowledged functions such as neuroprotection and even neurogenesis itself. Most recently, the neurogenesis function has attracted much attention, and a number of research groups have taken up the challenge of elucidating this activity. In keeping with this trend, our knowledge of VEGF receptors has increased, and certain suggestions concerning the mechanisms of neuroprotection have come to light in the course of the ongoing work, though at times what the researchers had to work with was only a tiny percent of the signal transduction of VEGF. Together with flt-1 (VEGF receptor 1) and flk-1 (VEGF receptor 2), neuropilin (NP) is frequently described as being involved in the neuroprotective effects of VEGF. In this review, both the direct and indirect neuroprotective effects of VEGF, including various signaling pathways as well as the neurogenesis induced by this factor, are discussed in the context of the newly emerging insights into the biological mechanisms of VEGF and closely related, interacting molecules.

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  • Glioblastoma with metastasis to the spleen--case report.

    Takao Yasuhara, Takashi Tamiya, Toshinari Meguro, Tomotsugu Ichikawa, Yumiko Sato, Isao Date, Hiroyuki Nakashima, Takashi Ohmoto

    Neurologia medico-chirurgica   43 ( 9 )   452 - 6   2003年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 47-year-old woman presented with headache and left homonymous hemianopsia. T1-weighted magnetic resonance (MR) imaging with contrast medium showed a mass lesion with ring-like enhancement in the right temporo-occipital lobe. The patient underwent surgery, focal irradiation, and chemotherapy. The histological diagnosis was glioblastoma. Four months after the operation, the patient again developed headache and left homonymous hemianopsia in addition to vomiting and mild left hemiparesis. MR imaging showed recurrence of the tumor and hydrocephalus. The patient underwent a second craniotomy and placement of a ventriculoperitoneal shunt. Intraoperative findings revealed that the transverse-sigmoid sinus was occluded by tumor invasion. The patient died of intraventricular dissemination 2 months after the second operation. Autopsy revealed metastases in the spleen and lungs. Glioblastoma with metastases to the spleen is very rare. The prognosis for patients is poor. Excessive therapy should not be used for patients with extracranial metastases from glioblastoma.

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  • 自然血栓化した後大脳動脈末梢部紡錘状動脈瘤の1例

    近藤聡彦, 安原隆雄, 杉生憲志, 大本堯史

    脳神経外科   31 ( 2 )   189 - 93   2003年2月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Wegener granulomatosis manifesting as meningitis. Case report. 国際誌

    Takao Yasuhara, Toru Fukuhara, Minoru Nakagawa, Yoshinori Terai, Kimihiro Yoshino, Koichi Mizobuchi, Shunichiro Fujimoto

    Journal of neurosurgery   97 ( 5 )   1229 - 32   2002年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The authors describe a unique presentation of Wegener granulomatosis (WG) manifesting predominantly as meningitis. Magnetic resonance imaging demonstrated diffuse meningeal enhancement, including the pia mater, in a 28-year-old man with meningitis. A diagnosis of atypical WG was based on the findings of a dural biopsy sample and an elevated cytoplasmic antineutrophil cytoplasmic antibody (cANCA) titer, although the patient did not have any of the lesions common to WG. Immunosuppressive therapy was quite effective. With treatment, the meningeal enhancement resolved and the cANCA titer normalized. Meningeal granulomatosis as the sole lesion in WG has never been reported in the literature. This atypical course of WG should be noted.

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  • De novo formation and rupture of an aneurysm. Case report. 国際誌

    Takao Yasuhara, Takashi Tamiya, Kenji Sugiu, Satoshi Inoue, Takashi Ohmoto

    Journal of neurosurgery   97 ( 3 )   697 - 700   2002年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The authors describe a case of de novo formation and rupture of an aneurysm located at the junction of the left internal carotid artery and the superior hypophyseal artery in a middle-aged woman 2 months after another aneurysm, located on the anterior communicating artery, had been clipped. This case is rare because of the short interval between the last angiographic study performed at the first operation and the diagnosis of the de novo aneurysm; in this case the interval was only 47 days, compared with other cases in the literature in which the intervals were 3 to 34 years. Aneurysms can enlarge considerably in 2 to 4 weeks and can rupture at or soon after their formation. This case provides insight into aneurysm formation and rupture.

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▼全件表示

書籍等出版物

  • 脳神経外科手術のための術後感染症予防 実践マニュアル

    宮本 享 監修 井川房夫、三國信啓、森田明夫 編集( 担当: 共著 ,  範囲: 脊椎脊髄外科領域)

    メジカルビュー  2021年  ( ISBN:9784758318570

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    担当ページ:96-107   記述言語:日本語

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  • 脳神経外科手術 基本主義のバリエーションー手術のWEB動画55本付きー(脳神経外科速報 2021年増刊)

    大宅宗一 監修、竹田理々子 編集( 担当: 共著 ,  範囲: 「超音波手術器派」の立場からー頭蓋底骨削除の方法(ハイスピードドリルまたは超音波手術器))

    メディカ出版  2021年  ( ISBN:9784840473460

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    総ページ数:268   担当ページ:233-236   記述言語:日本語

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  • 疾患・術式別 脳神経外科手術合併症の回避・対処法Q & A 156

    吉村紳一 監修、吉本幸司 編集( 担当: 共著 ,  範囲: 脊椎固定術における隣接椎間傷害について教えてください─脊椎・脊髄手術:腰椎─)

    メディカ出版  2019年 

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    担当ページ:234-235   記述言語:日本語

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  • 脳腫瘍外科 経験したい手術16─スタンダードからアドバンス─

    中尾直之、井川房夫 編集( 担当: 共著 ,  範囲: 大脳鎌髄膜腫─手術の実際 テント上浅部腫瘍─)

    メジカルビュー社  2019年 

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    総ページ数:355   担当ページ:103-117   記述言語:日本語

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  • 再生医療の開発戦略と最新研究事例集

    技術情報協会 編集( 担当: 共著 ,  範囲: パーキンソン病における治療の現状と再生医療等製品ニーズ─臓器・器官、疾病ごとの治療・製品ニーズの把握と製品開発─)

    技術情報協会  2019年 

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    総ページ数:420   担当ページ:74-80   記述言語:日本語

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  • 疾患・術式別 脳神経外科手術合併症の回避・対処法Q & A 156

    吉村紳一 監修、吉本幸司 編集( 担当: 共著 ,  範囲: 硬膜損傷してしまった!どうすればよいですか?─脊椎・脊髄手術:腰椎─)

    メディカ出版  2019年 

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    担当ページ:229-230   記述言語:日本語

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  • 疾患・術式別 脳神経外科手術合併症の回避・対処法Q & A 156

    吉村紳一 監修、吉本幸司 編集( 担当: 共著 ,  範囲: 脊椎手術における皮膚障害対策をどうしていますか?─脊椎・脊髄手術:腰椎─)

    メディカ出版  2019年 

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    担当ページ:232-233   記述言語:日本語

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  • 疾患・術式別 脳神経外科手術合併症の回避・対処法Q & A 156

    吉村紳一 監修、吉本幸司 編集( 担当: 共著 ,  範囲: 脊椎手術の感染症(SSI)対策をどうしていますか?─脊椎・脊髄手術:腰椎─)

    メディカ出版  2019年 

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    担当ページ:231   記述言語:日本語

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  • 疾患・術式別 脳神経外科手術合併症の回避・対処法Q & A 156

    吉村紳一 監修、吉本幸司 編集( 担当: 共著 ,  範囲: Instrumentation failureにはどう対処しますか?─脊椎・脊髄手術:腰椎─)

    メディカ出版  2019年 

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    担当ページ:236-237   記述言語:日本語

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  • 第32回微小脳神経外科解剖研究会 講演集

    香川大学医学部脳神経外科 編集( 担当: 共著 ,  範囲: 微小脳神経外科解剖をリアルに理解する─臨床応用解剖の意義─)

    メッド  2018年 

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    総ページ数:70   担当ページ:35-37   記述言語:日本語

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  • 新NS NOW No.16 Neurosurgical Re-Operations─脳神経外科における再手術・再治療─

    森田明夫 担当編集員、森田明夫、伊達 勲、菊田健一郎 編集( 担当: 共著 ,  範囲: 再手術判断に必要な画像・臨床診断)

    メジカルビュー社  2018年 

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    総ページ数:183   担当ページ:18-30   記述言語:日本語

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  • 新NS NOW No.9 デバイスとITを使いこなす脳神経外科手術─器具・機器を知ってテクニックに生かす─

    伊達 勲 担当編集委員 森田明夫、伊達 勲、菊田健一郎 編集( 担当: 共著 ,  範囲: 脊椎手術インストゥルメンテーション─安全な椎弓根スクリュー刺入のために─)

    メジカルビュー社  2017年 

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    担当ページ:78-91   記述言語:日本語

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  • 神経疾患 最新の治療 2015-2017

    小林祥泰、水澤英洋、山口修平 編( 担当: 共著 ,  範囲: 後縦靭帯骨化症(OPLL)、黄色靭帯骨化症(OYL))

    南江堂  2015年 

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    担当ページ:181-184   記述言語:日本語

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  • Geriatric Neurosurgery Vol.26

    小林 秀 監修、松岡浩司 編( 担当: 共著 ,  範囲: 高齢者に対する化膿性脊椎炎の治療[短報])

    日本老年脳神経外科学会事務局  2014年 

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    担当ページ:117-120   記述言語:日本語

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  • 第3回研究会記録集 日本整容脳神経外科研究会

    渡辺英寿( 担当: 共著 ,  範囲: 研究報告例─腰椎手術における小さくきれいな術創への工夫─)

    自治医科大学脳神経外科  2011年 

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    担当ページ:66-68   記述言語:日本語

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  • Methods in Bioengineering: Cell Transplantation

    Soto-Gutierrez A, Navarro-Alvarez N, Fox IJ( 担当: 共著 ,  範囲: Cell Transplantation and Regeneration in Neurology)

    Artech House  2011年 

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    担当ページ:121-130   記述言語:英語

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  • 脳腫瘍の外科─社会が望む脳腫瘍外科─

    大畑建治 編( 担当: 共著 ,  範囲: 頭蓋底、トルコ鞍近傍疾患への神経内視鏡の適応と限界)

    ミックス大阪  2011年 

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    担当ページ:64-69   記述言語:日本語

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  • サイエンスマップ2008 (NISTEP REPORT No.139)

    阪 彩香、伊神正貫、桑原輝隆 調査( 担当: 共著 ,  範囲: パーキンソン病に対する臨床研究)

    文部科学省 科学技術政策研究所 科学技術基盤調査研究室  2010年 

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    担当ページ:130-130   記述言語:日本語

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  • Geriatric Neurosurgery Vol.21

    原岡 襄監修、三木 保編集( 担当: 共著 ,  範囲: 骨粗鬆症性脊椎椎体圧迫骨折に対する経皮的椎体形成術の治療成績)

    日本老年脳神経外科学会事務局  2009年 

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    担当ページ:227-231   記述言語:日本語

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  • Birth, Life and Death of Dopaminergic Neurons in the Substantia Nigra

    G.Di Giovanni, V. Di Matteo, E. Esposito( 担当: 共著 ,  範囲: Gene Therapy for Parkinson's Disease)

    Springer  2009年 

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    担当ページ:301-309   記述言語:英語

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  • 第1回研究会記録集 日本整容脳神経外科研究会

    寺本 明( 担当: 共著 ,  範囲: 頭蓋底外科後の整容に関わる問題点─問題回避のための手術の工夫を中心に─)

    日本医科大学脳神経外科  2009年 

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    担当ページ:29-30   記述言語:日本語

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  • NS NOW No.3 テント上髄膜腫─アプローチから摘出まで─

    新井 一、寺本 明、塩川芳昭、大畑建治編( 担当: 共著 ,  範囲: 大脳鎌髄膜腫)

    メジカルビュー社  2008年 

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    担当ページ:64-72   記述言語:日本語

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  • Advances in Alzheimer's and Parkinson's Disease

    Abraham Fisher, Maurizio Memo, Fabrizio Stocchi, Israel Hanin eds.( 担当: 共著 ,  範囲: Neurotransmitter and neurotrophic factor-secreting cell line grafting for the treatment of Parkinson's disease)

    Springer  2008年 

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    担当ページ:51-56   記述言語:英語

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  • Minimally Invasive Neurosurgery and Multidisciplinary Neurotraumatology

    Kanno T, Kato Y (eds)( 担当: 共著 ,  範囲: Genetically modified cell line grafting for the treatment of Parkinson's disease)

    Springer-Verlag Tokyo  2006年 

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    担当ページ:108-113   記述言語:英語

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  • Minimally Invasive Neurosurgery and Multidisciplinary Neurotraumatology

    Kanno T, Kato Y (eds)( 担当: 共著 ,  範囲: Neuroprotection and repair by using adult-derived neural stem cell grafting for neurological disorders)

    Springer-Verlag Tokyo  2006年 

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    担当ページ:131-137   記述言語:英語

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  • Cell transplantation from laboratory to clinic

    Emerich DF( 担当: 共著 ,  範囲: NT2N cell transplantation and GDNF treatment in stroke)

    Academic Press  2006年 

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    担当ページ:1-19   記述言語:英語

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  • ファーマナビゲーター脳卒中編

    井林雪郎編( 担当: 共著 ,  範囲: 脳卒中再生医療の現状と未来は?)

    メディカルレビュー社  2006年 

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    担当ページ:510-514   記述言語:日本語

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  • 先端医療シリーズ29・脳神経外科 脳神経外科の最新医療

    菊池晴彦監修( 担当: 共著 ,  範囲: 細胞移植療法─パーキンソン病、脳虚血を中心に─)

    先端医療技術研究所  2004年 

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    担当ページ:56-63   記述言語:日本語

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  • Molecular mechanism and epochal therapeutics of ischemic stroke and dementia

    Abe, K.( 担当: 共著 ,  範囲: Cell therapy for cerebral ischemia using vascular endothelial growth factor-secreting cells)

    Elsevier Science B.V  2003年 

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    担当ページ:483-487   記述言語:英語

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▼全件表示

MISC

  • 三叉神経痛に対して牛車腎気丸および柴苓湯の併用が有効であった1例

    小川敦, 小川敦, 牛尾聡一郎, 亀田雅博, 亀田雅博, 横木梓, 椋田千晶, 江角悟, 渡邊亜津子, 村川公央, 安原隆雄, 北村佳久, 伊達勲, 千堂年昭

    医療薬学   47 ( 8 )   2021年

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  • Cerebral circulation improves with indirect bypass surgery combined with gene therapy

    Alex Shear, Shingo Nishihiro, Tomohito Hishikawa, Masafumi Hiramatsu, Kenji Sugiu, Takao Yasuhara, Isao Date

    BRAIN CIRCULATION   5 ( 3 )   119 - 123   2019年7月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WOLTERS KLUWER MEDKNOW PUBLICATIONS  

    Angiogenesis involves new blood vessels sprouting from preexisting blood vessels. This process may serve to improve brain circulation. Moyamoya disease (MMD) is a cerebrovascular disorder causing intracranial stenosis which significantly reduces the blood supply to the brain. Mainly stroke is the first symptom of the disorder, so treatments that reduce the risk of stroke are used for patients with MMD. To prevent stroke for those with chronic cerebral hypoperfusion, more blood needs to flow to the brain, which was thought to be achieved by enhancing angiogenesis. Indirect bypass surgery, such as encephalo-myo-synangiosis (EMS), is used for revascularization. However, EMS alone sometimes cannot provide enough circulation to avoid ischemic strokes. The current study examined if EMS combined with high-mobility group box-1 (HMGB1) and vascular endothelial growth factor (VEGF) enhanced angiogenesis and increased cerebral circulation. The results indicated that HMGB1 administered with EMS increased angiogenesis through a VEGF-dependent mechanism. In addition, exercising and stem cell transplantation possess possible means to increase angiogenesis. Overall, EMS with gene therapy, maintaining fitness, and stem cell utilization may prevent or help one recover from stroke by enhancing brain angiogenesis. Thus, these treatments may be applicable for patients with MMD. This paper is a review article. Referred literature in this paper has been listed in the references section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed.

    DOI: 10.4103/bc.bc_33_19

    Web of Science

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  • Electrical Stimulation Enhances Migratory Ability of Transplanted Bone Marrow Stromal Cells in a Rodent Ischemic Stroke Model. 国際誌

    Jun Morimoto, Takao Yasuhara, Masahiro Kameda, Michiari Umakoshi, Ittetsu Kin, Ken Kuwahara, Kyohei Kin, Mihoko Okazaki, Hayato Takeuchi, Tatsuya Sasaki, Atsuhiko Toyoshima, Naoki Tajiri, Takashi Agari, Cesario V Borlongan, Isao Date

    Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology   46 ( 1 )   57 - 68   2018年

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    記述言語:英語  

    BACKGROUND/AIMS: Bone marrow stromal cells (BMSCs) transplantation is an important strategy for the treatment of ischemic stroke. Currently, there are no effective methods to guide BMSCs toward the targeted site. In this study, we investigated the effect of electrical stimulation on BMSCs migration in an ischemic model of rats. METHODS: Adult male Wistar rats weighing 200 to 250 g received right middle cerebral artery occlusion (MCAO) for 90 minutes. BMSCs (2.5×105 cells/ 4 µl PBS) were stereotaxically injected into the left corpus callosum at 1 day after MCAO. After BMSCs injection, a plate electrode with a diameter of 3 mm connected to an implantable electrical stimulator was placed on the right frontal epidural space and a counter electrode was placed in the extra-cranial space. Electrical stimulation at preset current (100 µA) and frequency (100 Hz) was performed for two weeks. Behavioral tests were performed at 1, 4, 8, and 15 days after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at 15 days after MCAO for evaluation of infarction area and the migration distance and area of BMSCs found in the brain tissue. After evaluating cell migration, we proceeded to explore the mechanisms guiding these observations. MCAO rats without BMSCs transplantation were stimulated with same current and frequency. At 1 and 2 weeks after MCAO, rats were euthanized to evaluate stromal cell-derived factor 1 alpha (SDF-1α) level of brain tissues in the bilateral cortex and striatum. RESULTS: Behavioral tests at 4, 8, and 15 days after MCAO revealed that stimulation group displayed significant amelioration in mNSS and cylinder test compared to control group (p<0.05). Similarly, the infarction areas of stroke rats in stimulation group were significantly decreased compared to control group (p<0.05). Migration distance and area of transplanted BMSCs were significantly longer and wider respectively in stimulation group. An increased concentration gradient of SDF-1α in stimulation group accompanied this enhanced migration of transplanted cells. CONCLUSIONS: These results suggest that electrical stimulation enhances migratory ability of transplanted BMSCs in ischemic stroke model of rats. If we can direct the implanted BMSCs to the site of interest, it may lead to a greater therapeutic effect.

    DOI: 10.1159/000488409

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  • A case of very long longitudinally extensive transverse myelitis (LETM) with necrotizing Vasculitis 国際誌

    Kota Sato, Keiichiro Tsunoda, Toru Yamashita, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Toshiyuki Takahashi, Ichiro Nakashima, Takao Yasuhara, Isao Date, Koji Abe

    Journal of the Neurological Sciences   373   152 - 154   2017年2月

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  • パーキンソン病と再生医療 (特集 再生医療とリハビリテーション)

    安原 隆雄, 田尻 直輝, 伊達 勲

    総合リハビリテーション   45 ( 1 )   21 - 26   2017年1月

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    記述言語:日本語   出版者・発行元:医学書院  

    CiNii Article

    CiNii Books

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  • Prognostic impact of radiation therapy and molecular classification of infant atypical teratoid/rhabdoid tumors

    Yoshihiro Otani, Tomotsugu Ichikawa, Kazuhiko Kurozumi, Takao Yasuhara, Kana Washio, Akira Shimada, Norihisa Katayama, Kuniaki Katsui, Hiroyuki Yanai, Isao Date

    Neurological Surgery, No shinkei geka. Neurological surgery   45 ( 2 )   147 - 154   2017年

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    記述言語:日本語  

    DOI: 10.11477/mf.1436203466

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  • 乳児Atypical teratoid/rhabdid tumorに対する放射線治療および分子生物学的分類と予後との関連について.

    大谷理浩, 市川智継, 黒住和彦, 安原隆雄, 鷲尾佳奈, 嶋田 明, 片山敬久, 勝井邦彰, 柳井広之, 伊達 勲

    脳神経外科   45 ( 2 )   147 - 154   2017年

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  • 摘出術前の腫瘍栄養血管塞栓術が有用であった馬尾血管芽腫の1例

    馬越通有, 安原隆雄, 三好康之, 平松匡文, 豊嶋敦彦, 佐々田晋, 守本 純, 菱川朋人, 眞鍋博明, 徳永浩司, 杉生憲志, 伊達 勲

    脊髄外科   29 ( 1 )   53 - 58   2015年

  • No pain, no gain: lack of exercise obstructs neurogenesis. 国際誌

    Nate Watson, Xunming Ji, Takao Yasuhara, Isao Date, Yuji Kaneko, Naoki Tajiri, Cesar V Borlongan

    Cell transplantation   24 ( 4 )   591 - 7   2015年

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    記述言語:英語  

    Bedridden patients develop atrophied muscles, their daily activities greatly reduced, and some display a depressive mood. Patients who are able to receive physical rehabilitation sometimes show surprising clinical improvements, including reduced depression and attenuation of other stress-related behaviors. Regenerative medicine has advanced two major stem cell-based therapies for CNS disorders, namely, transplantation of exogenous stem cells and amplification of endogenous neurogenesis. The latter strategy embraces a natural way of reinnervating the damaged brain and correcting the neurological impairments. In this study, we discussed how immobilization-induced disuse atrophy, using the hindlimb suspension model, affects neurogenesis in rats. The overarching hypothesis is that immobilization suppresses neurogenesis by reducing the circulating growth or trophic factors, such as vascular endothelial growth factor or brain-derived neurotrophic factor. That immobilization alters neurogenesis and stem cell differentiation in the CNS requires characterization of the stem cell microenvironment by examining the trophic and growth factors, as well as stress-related proteins that have been implicated in exercise-induced neurogenesis. Although accumulating evidence has revealed the contribution of "increased" exercise on neurogenesis, the reverse paradigm involving "lack of exercise," which mimics pathological states (e.g., stroke patients are often immobile), remains underexplored. This novel paradigm will enable us to examine the effects on neurogenesis by a nonpermissive stem cell microenvironment likely produced by lack of exercise. BrdU labeling of proliferative cells, biochemical assays of serum, cerebrospinal fluid and brain levels of trophic factors, growth factors, and stress-related proteins are proposed as indices of neurogenesis, while quantitative measurements of spontaneous movements will reveal psychomotor components of immobilization. Studies designed to reveal how in vivo stimulation, or lack thereof, alters the stem cell microenvironment are needed to begin to develop treatment strategies for enhancing neurogenesis in bedridden patients.

    DOI: 10.3727/096368915X687723

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  • Therapeutic outcomes of transplantation of amniotic fluid-derived stem cells in experimental ischemic stroke. 国際誌

    Naoki Tajiri, Sandra Acosta, Gabriel S Portillo-Gonzales, Daniela Aguirre, Stephanny Reyes, Diego Lozano, Mibel Pabon, Ike Dela Peña, Xunming Ji, Takao Yasuhara, Isao Date, Marianna A Solomita, Ivana Antonucci, Liborio Stuppia, Yuji Kaneko, Cesar V Borlongan

    Frontiers in cellular neuroscience   8   227 - 227   2014年

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    記述言語:英語  

    Accumulating preclinical evidence suggests the use of amnion as a source of stem cells for investigations of basic science concepts related to developmental cell biology, but also for stem cells' therapeutic applications in treating human disorders. We previously reported isolation of viable rat amniotic fluid-derived stem (AFS) cells. Subsequently, we recently reported the therapeutic benefits of intravenous transplantation of AFS cells in a rodent model of ischemic stroke. Parallel lines of investigations have provided safety and efficacy of stem cell therapy for treating stroke and other neurological disorders. This review article highlights the need for investigations of mechanisms underlying AFS cells' therapeutic benefits and discusses lab-to-clinic translational gating items in an effort to optimize the clinical application of the cell transplantation for stroke.

    DOI: 10.3389/fncel.2014.00227

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  • 頭蓋底悪性腫瘍摘出術における脳神経外科の役割

    安原隆雄, 黒住和彦, 市川智継, 小野成紀, 小野田友男, 江口元治, 山田 潔, 木股敬裕, 伊達 勲

    脳神経外科速報   24 ( 6 )   670 - 677   2014年

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  • Regenerative medicine for epilepsy: from basic research to clinical application. 国際誌

    Takao Yasuhara, Takashi Agari, Masahiro Kameda, Akihiko Kondo, Satoshi Kuramoto, Meng Jing, Tatsuya Sasaki, Atsuhiko Toyoshima, Susumu Sasada, Kenichiro Sato, Aiko Shinko, Takaaki Wakamori, Yu Okuma, Yasuyuki Miyoshi, Naoki Tajiri, Cesario V Borlongan, Isao Date

    International journal of molecular sciences   14 ( 12 )   23390 - 401   2013年11月

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    記述言語:英語  

    Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.

    DOI: 10.3390/ijms141223390

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  • In vivo animal stroke models: a rationale for rodent and non-human primate models. 国際誌

    Naoki Tajiri, Travis Dailey, Christopher Metcalf, Yusef I Mosley, Tsz Lau, Meaghan Staples, Harry van Loveren, Seung U Kim, Tetsumori Yamashima, Takao Yasuhara, Isao Date, Yuji Kaneko, Cesario V Borlongan

    Translational stroke research   4 ( 3 )   308 - 21   2013年6月

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    記述言語:英語  

    On average, every four minutes an individual dies from a stroke, accounting for 1 out of every 18 deaths in the United States. Approximately 795,000 Americans have a new or recurrent stroke each year, with just over 600,000 of these being first attack [1]. There have been multiple animal models of stroke demonstrating that novel therapeutics can help improve the clinical outcome. However, these results have failed to show the same outcomes when tested in human clinical trials. This review will discuss the current in vivo animal models of stroke, advantages and limitations, and the rationale for employing these animal models to satisfy translational gating items for examination of neuroprotective, as well as neurorestorative strategies in stroke patients. An emphasis in the present discussion of therapeutics development is given to stem cell therapy for stroke.

    DOI: 10.1007/s12975-012-0241-2

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  • 胸腰椎部硬膜動静脈瘻の術中所見と治療結果の検討

    三好康之, 安原隆雄, 眞鍋博明, 服部靖彦, 菱川朋人, 徳永浩司, 杉生憲志, 伊達 勲

    脊髄外科   27   45 - 51   2013年

  • パーキンソン病に対するSTN-DBSの術中せん妄における危険因子の検討

    新光 阿以子, 上利 崇, 近藤 聡彦, 佐々木 達也, 佐々田 晋, 金 恭平, 若森 孝彰, 亀田 雅博, 安原 隆雄, 伊達 勲

    機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery   52   135 - 139   2013年

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    記述言語:日本語   出版者・発行元:日本定位・機能神経外科学会事務局  

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  • The potential of carbamylated erythropoietin fusion protein in a rat model of Parkinson's disease

    Tayra Judith Thomas, Kameda Masahiro, Yasuhara Takao, Agari Takashi, Kadota Tomohito, Wang Feifei, Kikuchi Yoichiro, Shinko Aiko, Wakamori Takaaki, Sasaki Tatsuya, Sasada Susumu, Toyoshima Atsuhiko, Takeuchi Hayato, Vcelar Brigitta, Weik Robert, Date Isao

    機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery   52   97 - 102   2013年

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    記述言語:英語   出版者・発行元:日本定位・機能神経外科学会事務局  

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    その他リンク: http://search.jamas.or.jp/link/ui/2014281141

  • 重症下肢虚血に対するSCSの有効性

    佐々木 達也, 上利 崇, 有澤 正, 中濱 一, 太田 壮, 竹内 亮, 新光 阿以子, 佐々田 晋, 若森 孝彰, 近藤 聡彦, 亀田 雅博, 安原 隆雄, 伊達 勲

    機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery   52   88 - 92   2013年

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    記述言語:日本語   出版者・発行元:日本定位・機能神経外科学会事務局  

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    その他リンク: http://search.jamas.or.jp/link/ui/2014281139

  • 進行期パーキンソン病患者における認知機能低下

    若森 孝彰, 上利 崇, 近藤 聡彦, 新光 阿以子, 佐々田 晋, 佐々木 達也, 亀田 雅博, 安原 隆雄, 伊達 勲

    機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery   52   93 - 96   2013年

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    記述言語:日本語   出版者・発行元:日本定位・機能神経外科学会事務局  

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    その他リンク: http://search.jamas.or.jp/link/ui/2014281140

  • 視床手術での標的決定における diffusion tensor imaging を用いた fiber tractography の有用性

    佐々田 晋, 上利 崇, 丸尾 智子, 金 恭平, 佐々木 達也, 新光 阿以子, 若森 孝彰, 近藤 聡彦, 亀田 雅博, 安原 隆雄, 衣笠 和孜, 伊達 勲

    機能的脳神経外科 : 日本定位・機能神経外科学会機関誌 = Functional neurosurgery : official journal of the Japan Society for Stereotactic and Functional Neurosurgery   52   82 - 87   2013年

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    記述言語:日本語   出版者・発行元:日本定位・機能神経外科学会事務局  

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    その他リンク: http://search.jamas.or.jp/link/ui/2014281138

  • Intravenous grafts of amniotic fluid-derived stem cells induce endogenous cell proliferation and attenuate behavioral deficits in ischemic stroke rats. 国際誌

    Naoki Tajiri, Sandra Acosta, Loren E Glover, Paula C Bickford, Alejandra Jacotte Simancas, Takao Yasuhara, Isao Date, Marianna A Solomita, Ivana Antonucci, Liborio Stuppia, Yuji Kaneko, Cesar V Borlongan

    PloS one   7 ( 8 )   e43779   2012年

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    記述言語:英語  

    We recently reported isolation of viable rat amniotic fluid-derived stem (AFS) cells [1]. Here, we tested the therapeutic benefits of AFS cells in a rodent model of ischemic stroke. Adult male Sprague-Dawley rats received a 60-minute middle cerebral artery occlusion (MCAo). Thirty-five days later, animals exhibiting significant motor deficits received intravenous transplants of rat AFS cells or vehicle. At days 60-63 post-MCAo, significant recovery of motor and cognitive function was seen in stroke animals transplanted with AFS cells compared to vehicle-infused stroke animals. Infarct volume, as revealed by hematoxylin and eosin (H&E) staining, was significantly reduced, coupled with significant increments in the cell proliferation marker, Ki67, and the neuronal marker, MAP2, in the dentate gyrus (DG) [2] and the subventricular zone (SVZ) of AFS cell-transplanted stroke animals compared to vehicle-infused stroke animals. A significantly higher number of double-labeled Ki67/MAP2-positive cells and a similar trend towards increased Ki67/MAP2 double-labeling were observed in the DG and SVZ of AFS cell-transplanted stroke animals, respectively, compared to vehicle-infused stroke animals. This study reports the therapeutic potential of AFS cell transplantation in stroke animals, possibly via enhancement of endogenous repair mechanisms.

    DOI: 10.1371/journal.pone.0043779

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  • 顕微鏡手術における神経内視鏡の役割─神経内視鏡と顕微鏡の使い分けの現状分析を中心に─.

    小野成紀, 石田穣治, 安原隆雄, 黒住和彦, 市川智継, 伊達 勲

    脳神経外科ジャーナル   20 ( 10 )   716 - 724   2011年

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  • 脊髄くも膜下出血後Adamkiewicz動脈に生じた血管攣縮.

    三好康之, 近藤聡彦, 安原隆雄, 西田あゆみ, 徳永浩司, 杉生憲志, 伊達 勲

    BRAIN and NERVE   63 ( 2 )   182 - 183   2011年

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  • パーキンソン病モデルラットにおける病態を示すバイオマーカーとしての尿中8-OHdGの変化

    菊池 陽一郎, 上利 崇, 安原 隆雄, 藏本 智士, 近藤 聡彦, 亀田 雅博, 門田 知倫, 田尻 直輝, 馬場 胤典, 王 飛霏, タイラ ジュディッチ・トーマス, 三好 康之, 伊達 勲

    Functional neurosurgery : proceedings of the annual meeting of the Japan Society for Stereotactic and Functional Neurosurgery   49 ( 1 )   66 - 67   2010年6月

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  • パーキンソン病に対する遺伝子治療 : ex vivo 遺伝子治療を中心に

    安原 隆雄, 上利 崇, 近藤 聡彦, 田尻 直輝, 王 飛霏, 馬場 胤典, 三好 康之, 原 晃一, BORLONGAN Cesario V., 伊達 勲

    Functional neurosurgery : proceedings of the annual meeting of the Japan Society for Stereotactic and Functional Neurosurgery   48 ( 1 )   2 - 3   2009年6月

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  • 脳梗塞に対するgene therapy

    安原隆雄, 田尻直輝, 王Feifei, 馬場胤典, 門田知倫, Liang Hanbai, Judith Thomas Tayra, 菊池陽一郎, 村岡賢一郎, 亀田雅博, 上利崇, 近藤聡彦, 菱川朋人, 小野成紀, 三好康之, 徳永浩司, 伊達 勲

    脳卒中   31   420 - 424   2009年

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  • 定位脳手術の既往のあるパーキンソン病患者に対する視床下核刺激療法.

    松井利浩, 上利 崇, 藏本智士, 安原隆雄, 新郷哲郎, 三好康之, 伊達 勲

    機能的脳神経外科   2004年

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▼全件表示

講演・口頭発表等

  • 頭部外傷後West症候群に対して半球離断術を施行した1例

    駿河和城、佐々木達也、米田 哲、亀田雅博、安原隆雄、柴田 敬、小林勝弘、伊達 勲

    第90回(一社)日本脳神経外科学会中国四国支部学術集会  2020年12月  川崎医科大学 脳神経外科

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    開催年月日: 2021年12月5日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 胸椎脊髄ヘルニアの硬膜欠損に対して、DuraGen を用いた1例

    佐々田晋、安原隆雄、松田勇輝、伊達 勲

    第92回(一社)日本脳神経外科学会中国四国支部学術集会  2021年12月4日  高知大学医学部 脳神経外科

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    開催年月日: 2021年12月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:高知  

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  • Cone-beam CTを用いたlateral spinal arteryの正常解剖と頭蓋頚椎移行部動静脈瘻の血管解剖の解析(シンポジウム)

    平松匡文、杉生憲志、安原隆雄、菱川朋人、春間 純、村井 智、西 和彦、山岡陽子、佐藤 悠、胡谷侑貴、伊達 勲

    第37回NPO法人日本脳神経血管内治療学会学術集会(現地・Web併催)  2021年11月27日  福岡大学筑紫病院 脳神経外科

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    開催年月日: 2021年11月25日 - 2021年11月27日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:福岡  

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  • 脳脊髄動静脈シャント疾患の罹患率に対して地域性が与える影響

    村井 智、 高杉祐二、平松匡文、鈴木越治、石橋良太、宮崎裕子、春間 純、菱川朋人、安原隆雄、杉生憲志、伊達 勲

    第37回NPO法人日本脳神経血管内治療学会学術集会(現地・Web併催)  2021年11月25日  福岡大学筑紫病院 脳神経外科

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    開催年月日: 2021年11月25日 - 2021年11月27日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:福岡  

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  • げっ歯類を用いた虚血再灌流障害の機序研究

    大熊 佑、篠崎広一郎、林田 敬、トレイシー ケビン、菱川朋人、安原隆雄、大同 茂、伊達 勲、ベッカー ランス

    第37回NPO法人日本脳神経血管内治療学会学術集会(現地・Web併催)  2021年11月25日  福岡大学筑紫病院 脳神経外科

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    開催年月日: 2021年11月25日 - 2021年11月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:福岡  

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  • Osseous involvementを伴う脊髄硬膜外動静脈瘻(シンポジウム)

    平松匡文、杉生憲志、安原隆雄、伊達 勲

    第37回NPO法人日本脳神経血管内治療学会学術集会(現地・Web併催)  2021年11月25日  福岡大学筑紫病院 脳神経外科

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    開催年月日: 2021年11月25日 - 2021年11月27日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:福岡  

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  • 聴神経腫瘍における初回治療後の増大因子の検討

    牧野圭悟、大谷理浩、藤井謙太郎、石田穣治、畝田篤仁、坪井伸成、平野秀一郎、劒持直也、駿河和城、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月29日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • 脊椎・脊髄腫瘍手術の執刀医になるために─術前検討から難局打破の一手まで─(ビデオシンポジウム)

    安原隆雄、佐々田晋、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月29日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:横浜  

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  • 多機能を有する脳深部刺激療法デバイスの最適な刺激設定と調節法の検討

    佐々木達也、皮居巧嗣、岡崎洋介、細本 翔、佐々田晋、安原隆雄、上利 崇、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月29日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • 迷走神経求心路刺激・遠心路刺激のパーキンソン病モデルラットに対する有効性

    細本 翔、佐々木達也、皮居巧嗣、永瀬喬之、菅原千明、岡崎洋介、藪野 諭、河内 哲、冨田陽介、金 一徹、桑原 研、佐々田晋、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月28日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • 虚血再灌流障害急性期におけるnear-infrared spectroscopyでのモニタリングの有用性 国際共著

    大熊 佑、篠崎光一郎、林田 敬、J Kevin Traccy、菱川朋人、安原隆雄、大同 茂、伊達 勲、B Lance Becker

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 頭蓋骨の高度な肥厚に伴い後頭蓋窩狭小化を来たし、外科治療を要した2例

    佐々田晋、安原隆雄、河内 哲、菅原千明、藪野 諭、冨田陽介、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 脳梗塞モデルラットに対するカプセル化ヒト骨髄由来間葉系幹細胞の脳内移植による治療効果の検討

    河内 哲、安原隆雄、佐々田晋、冨田陽介、藪野 諭、菅原千明、長瀬、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • ラット脳虚血モデルへのヒト骨髄由来多能性幹細胞(SB623)の脳内移植とリハビリテーションの相乗効果の検討

    藪野 諭、安原隆雄、河内 哲、菅原千明、永瀬喬之、細本 翔、岡崎洋介、皮居巧嗣、冨田陽介、佐々木達也、佐々田晋、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 神経症状の急激な悪化により緊急・準緊急を要した非骨傷性脊椎脊髄疾患症例の検討

    菅原千明、安原隆雄、佐々田晋、冨田陽介、河内 哲、藪野 諭、永瀬喬之、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • てんかんモデルラットに対する持続硬膜外脊髄刺激療法の検討

    岡崎洋介、佐々木達也、皮居巧嗣、永瀬喬之、菅原千明、藪野 諭、細本 翔、河内 哲、冨田陽介、金 一徹、桑原 研、佐々田晋、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • RB1遺伝子germline変異を伴う放射線誘発骨肉腫に対する広範囲頭蓋底腫瘍摘出・再建術 招待

    松田勇輝、大谷理浩、安原隆雄、安藤瑞生、檜垣貴哉、牧野琢丸、松本 洋、大山矩史、西森久和、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:横浜  

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    永瀬喬之、石田穣治、佐々田晋、佐々木達也、大谷理浩、藪野 諭、藤井謙太郎、畝田篤仁、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第80回学術総会(現地・Web併催)  2021年10月27日  山梨大学医学部 脳神経外科

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    開催年月日: 2021年10月27日 - 2021年10月30日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 中大脳動脈閉塞モデルラットに対するカプセル化ヒト骨髄由来間葉系幹細胞の脳内移植による治療効果の検討

    河内 哲、安原隆雄、佐々田晋、冨田陽介、藪野 諭、菅原千明、永瀬喬之、佐々木達也、伊達 勲

    第21回日本分子脳神経外科学会(Web開催)  2021年9月25日  京都府立医科大学 脳神経外科

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    開催年月日: 2021年9月24日 - 2021年9月25日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 基礎研究ー臨床研究ー実臨床 つながる脳神経外科:ベリプラスト Pコンビセットの使用法も交えて(イブニングセミナー) 招待

    安原隆雄

    第21回日本分子脳神経外科学会(Web開催)  2021年9月24日  京都府立医科大学 脳神経外科

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    開催年月日: 2021年9月24日 - 2021年9月25日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:京都  

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    佐々田晋、安原隆雄、藪野 諭、冨田陽介、永瀬喬之、菅原千明、河内 哲、伊達 勲

    第28回日本脊椎・脊髄神経手術手技学会学術集会(現地・Web併催)  2021年9月4日  関西医科大学 整形外科学

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    開催年月日: 2021年9月3日 - 2021年9月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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    佐々田晋、安原隆雄、藪野 諭、馬越通有、冨田陽介、河内 哲、伊達 勲

    第28回日本脊椎・脊髄神経手術手技学会学術集会(現地・Web併催)  2021年9月4日  関西医科大学 整形外科学

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    開催年月日: 2021年9月3日 - 2021年9月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 脊椎手術の骨削除における、超音波骨メスSonopet iQの使用経験

    佐々田晋、安原隆雄、小橋藍子、水田 亮、冨田陽介、平松匡文、伊達 勲

    第28回日本脊椎・脊髄神経手術手技学会学術集会(現地・Web併催)  2021年9月4日  関西医科大学 整形外科学

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    開催年月日: 2021年9月3日 - 2021年9月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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    佐々田晋、安原隆雄、守本 純、水田 亮、細本 翔、木村 颯、小川智之、小林和樹、伊達 勲

    第28回日本脊椎・脊髄神経手術手技学会学術集会(現地・Web併催)  2021年9月3日  関西医科大学 整形外科学

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    開催年月日: 2021年9月3日 - 2021年9月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 難治性癒着性くも膜炎に対するシャント治療

    安原隆雄、佐々田晋、伊達 勲

    第28回日本脊椎・脊髄神経手術手技学会学術集会(現地・Web併催)  2021年9月3日  関西医科大学 整形外科学

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    開催年月日: 2021年9月3日 - 2021年9月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 脊椎脊髄診療に軸足を置いた脳神経外科 招待

    安原隆雄

    第39回ニセコカンファレンス(現地・Web開催)  2021年8月21日  中村記念病院

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    開催年月日: 2021年8月21日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:札幌  

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  • 脳腫瘍関連てんかんに対する外科治療の手術戦略ー内側側頭葉てんかんと新皮質てんかんの違いについてー

    佐々木達也、細本 翔、岡 洋介、皮居巧嗣、佐々田晋、安原隆雄、伊達 勲

    第34回中国地方脳神経外科手術研究会(現地・Web開催)  2021年8月  広島市立広島市民病院

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    開催年月日: 2021年8月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:広島  

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  • 高度な後頭骨肥厚による狭小後頭蓋窩に対する外科治療

    安原隆雄、河内 哲、藪野 諭、菅原千明、冨田陽介、佐々田晋、伊達 勲

    第33回日本頭蓋底外科学会  2021年7月  東京大学大学院医学系研究科外科学専攻 感覚・運動機能医学講座 形成外科学分野

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    開催年月日: 2021年7月1日 - 2021年7月2日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 側頭葉てんかんの術後成績と再発例に対する再手術の検討

    佐々木達也、細本 翔、岡 洋介、皮居巧嗣、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第75回岡山てんかん懇話会(現地・Web開催)  2021年6月  岡山てんかん懇話会

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    開催年月日: 2021年6月24日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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    佐々田晋、守本 純、水田 亮、細本 翔、外間まどか、小川智之、安原隆雄、小林和樹

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • キアリ奇形・癒着性くも膜炎に関する再手術について(シンポジウム)

    安原隆雄、佐々田晋、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:京都  

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  • 脊椎脊髄手術における超音波手術器の可能性ー新型SONOPET iQの初期使用経験も交えてー(ランチョンセミナー) 招待

    安原隆雄、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:京都  

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    河内 哲、安原隆雄、菅原千明、藪野 諭、冨田陽介、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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    馬越通有、安原隆雄、村井 智、佐々木達也、河内 哲、藪野 諭、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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    藪野 諭、安原隆雄、菅原千明、河内 哲、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 脊髄腫瘍手術における技術的費用試算(シンポジウム)

    高見俊宏、安原隆雄、尾原裕康、金 彪

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:京都  

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    菅原千明、安原隆雄、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第36回日本脊髄外科学会(現地・Web開催)  2021年6月  社会医療法人信愛会 交野病院

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    開催年月日: 2021年6月3日 - 2021年6月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:京都  

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  • 腰椎変性疾患の治療ー「グローカル」な理解を実践(プレナリーセッション) 招待

    安原隆雄、伊達 勲

    第41回日本脳神経外科コングレス総会(現地・Web併催)  2021年5月  鹿児島大学大学院医歯学総合研究科 脳神経外科学

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    開催年月日: 2021年5月13日 - 2021年5月16日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:横浜  

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  • 脳神経外科・脊椎脊髄外科領域における手術の工夫(ランチョンセミナー) 招待

    安原隆雄

    第14回日本整容脳神経外科学会(Web開催)  2021年4月  札幌医科大学 脳神経外科

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    開催年月日: 2021年4月24日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:札幌  

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  • 脳神経外科・脊椎脊髄外科領域における手術の工夫(ランチョンセミナー) 招待

    安原隆雄

    第14回日本整容脳神経外科学会(Web開催)  2021年4月  札幌医科大学 脳神経外科

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    開催年月日: 2021年4月24日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:札幌  

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  • 80歳以上の超高齢者脊椎脊髄症例に対する手術をいかに安全に行うかー周術期管理センターの有用性ー(シンポジウム)

    安原隆雄、菱川朋人、藤井謙太郎、森松博史、伊達 勲

    第34回日本老年脳神経外科学会(Web開催)  2021年4月  秋田大学大学院医学系研究科 機能展開医学系 脳神経外科学

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    開催年月日: 2021年4月17日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:秋田  

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  • 光造形型3Dプリンタで作成した脳動脈瘤モデルでの術前シミュレーションが有用であった新規脳動脈瘤支援ステントデバイスPul

    春間 純、杉生憲志、胡谷侑貴、枝木久典、佐藤 悠、西 和彦、山岡陽子、村井 智、平松匡文、菱川朋人、安原隆雄、伊達 勲

    第91回(一社)日本脳神経外科学会中国四国支部学術集会(現地・Web併催)  2021年4月  島根大学医学部 脳神経外科

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    開催年月日: 2021年4月3日 - 2021年4月4日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:松江  

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  • 中枢神経系疾患に対する細胞移植療法・電気刺激療法・リハビリテーション(シンポジウム)

    安原隆雄、伊達 勲

    第126回日本解剖学会総会・全国学術集会、第98回日本生理学会大会 合同大会(Web開催)  2021年3月  名古屋大学大学院医学系研究科 機能組織学、脳神経生理学、細胞生理学

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    開催年月日: 2021年3月28日 - 2021年3月30日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:名古屋  

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  • 虚血再灌流障害急性期における高酸素投与の功罪

    大熊 佑、篠崎広一郎、林田 敬、トレーシー ケビン、菱川朋人、安原隆雄、大同 茂、伊達 勲、ベッカー ランス

    第46回日本脳卒中学会学術集会:STROKE 2021(現地・Web併催)  2021年3月  九州大学大学院医学研究院病態機能内科学

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    開催年月日: 2021年3月11日 - 2021年3月13日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:福岡  

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  • 転倒を契機に脊髄損傷となり、外科治療を要した頚椎病変の2症例

    菅原千明、安原隆雄、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第44回日本脳神経外傷学会(現地・Web開催)  2021年2月  香川大学医学部 脳神経外科

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    開催年月日: 2021年2月26日 - 2021年2月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:高松  

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  • 集中治療室管理を要した重症頭部外傷症例の長期予後(シンポジウム)

    安原隆雄、湯本哲也、村井 智、中尾篤典、伊達 勲

    第44回日本脳神経外傷学会(現地・Web開催)  2021年2月  香川大学医学部 脳神経外科

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    開催年月日: 2021年2月26日 - 2021年2月27日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:高松  

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  • 脊椎・脊髄外傷 これだけは知っておきたい!(教育講演) 招待

    安原隆雄

    第44回日本脳神経外傷学会(現地・Web開催)  2021年2月  香川大学医学部 脳神経外科

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    開催年月日: 2021年2月26日 - 2021年2月27日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:高松  

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  • 頭部外傷後West症候群に対して半球離断術を施行した1例

    岡崎洋介、佐々木達也、駿河和城、細本 翔、米田 哲、亀田雅博、安原隆雄、柴田 敬、小林勝弘、伊達 勲

    第15回日本てんかん学会中国・四国地方会(Web開催)  2021年2月  高知大学医学部 脳神経外科

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    開催年月日: 2021年2月20日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:高知  

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  • 脳梗塞モデルラットに対するカプセル化SB623脳内移植による治療効果の検討

    河内 哲、安原隆雄、亀田雅博、馬越通有、冨田陽介、藪野 諭、菅原千明、伊達 勲

    第46回岡山脳研究セミナー  2021年1月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2021年1月27日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • Rescue GPi-DBSが奏功したGNAO1遺伝子変異を有するジストニア重積の1例

    木村 颯、佐々木達也、兵頭勇紀、岡崎洋介、細本 翔、亀田雅博、安原隆雄、秋山倫之、伊達 勲

    第60回日本定位・機能神経外科学会(Web開催)  2021年1月  新潟大学脳研究所 脳神経外科学

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    開催年月日: 2021年1月22日 - 2021年1月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • 多機能を有する脳深部刺激療法デバイスの最適な刺激設定と調整法の検討(シンポジウム)

    佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、上利 崇、伊達 勲

    第60回日本定位・機能神経外科学会(Web開催)  2021年1月  新潟大学脳研究所 脳神経外科学

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    開催年月日: 2021年1月22日 - 2021年1月23日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:新潟  

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  • 両側淡蒼球内節刺激術が有効であったDYT1ジストニアの一卵性双胎例

    岡崎洋介、佐々木達也、細本 翔、亀田雅博、安原隆雄、秋山麻里、秋山倫之、小林勝弘、伊達 勲

    第60回日本定位・機能神経外科学会(Web開催)  2021年1月  新潟大学脳研究所 脳神経外科学

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    開催年月日: 2021年1月22日 - 2021年1月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • 迷走神経求心路刺激・遠心路刺激のパーキンソン病モデルラットに対する有効性

    細本 翔、佐々木達也、金 一徹、桑原 研、岡崎洋介、亀田雅博、安原隆雄、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第60回日本定位・機能神経外科学会(Web開催)  2021年1月  新潟大学脳研究所 脳神経外科学

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    開催年月日: 2021年1月22日 - 2021年1月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • 側頭葉てんかんの術後成績と再発例に対する再手術の検討

    細本 翔、佐々木達也、岡崎洋介、亀田雅博、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第44回日本てんかん外科学会(Web開催)  2021年1月  札幌医科大学 医学部脳神経外科

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    開催年月日: 2021年1月21日 - 2021年1月22日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • 限局性皮質異形成に対するてんかん外科手術の手術成績と発作時頭蓋内脳波の検討

    佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第44回日本てんかん外科学会(Web開催)  2021年1月  札幌医科大学 医学部脳神経外科

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    開催年月日: 2021年1月21日 - 2021年1月22日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • 当院における小児のてんかん外科手術の治療成績と神経発達の変化の検討

    岡崎洋介、佐々木達也、細本 翔、亀田雅博、安原隆雄、伊達 勲

    第44回日本てんかん外科学会(Web開催)  2021年1月  札幌医科大学 医学部脳神経外科

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    開催年月日: 2021年1月21日 - 2021年1月22日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:新潟  

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  • The basics of spinal surgery for degenerative diseases (Keynote Lecture) 招待

    Yasuahra T, Date I

    WFNS Foundation ACNS Cambodia, Myanmar, Thailand and Uzbekistan Joint Web Seminar 2020 (Webinar)  2020年12月 

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    開催年月日: 2020年12月18日

    記述言語:英語   会議種別:口頭発表(基調)  

    開催地:Web  

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  • ハイブリット開催の事例(国内会議)─日本脳神経外科学会第79回学術総会─ 招待

    安原隆雄

    一般社団法人日本コングレス・コンベンション・ビューロー(JCCB)特別企画セミナー─Withコロナ時代におけるMICEの促進について─(Web開催)  2020年12月  一般社団法人日本コングレス・コンベンション・ビューロー(JCCB

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    開催年月日: 2020年12月4日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:オンライン  

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  • 脳神経外科領域のSSIとその対策(シンポジウム) 招待

    安原隆雄、井川房夫、伊達 勲

    第33回日本外科感染症学会総会(Web開催)  2020年11月  防衛医科大学

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    開催年月日: 2020年11月27日 - 2020年11月28日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:東京  

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  • ラット中大脳動脈閉塞モデルにおけるcrossed cerebellar diaschisis

    西 和彦、木谷尚哉、杉生憲志、菱川朋人、安原隆雄、平松匡文、西廣真吾、高橋 悠、村井 智、山岡陽子、佐藤 悠、胡谷侑貴、伊達 勲

    第63回日本脳循環代謝学会学術集会(現地・Web併催)  2020年11月  東海大学医学部 神経内科

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    開催年月日: 2020年11月13日 - 2020年11月14日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 80歳以上の高齢者脊椎症例に対する手術周術期の問題点と対策

    菅原千明、安原隆雄、馬越通有、河内 哲、藪野 諭、伊達 勲

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • Co-existence of ossification of the posterior longitudinal ligament and arterio-cervical fistula at the cranio-cervical junction (Symposium)

    Sasada S, Hiramatu M, Kusumegi A, Fujimura H, Oshikata S, Takahashi Y, Yasuahra T, Nishida K

    The 11th Annual Meeting of Asia Spine (Virtual Meeting)  2020年11月  Tokyo Metropolitan Neurological Hospital

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:Tokyo  

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  • Treatment strategy for cervical spondylotic myelopathy: Opinion from a laminoplasty surgeon (Symposium)

    Yasuhara T, Umakoshi M, Kawauchi S, Yabuno S, Sugahara C, Date I

    The 11th Annual Meeting of Asia Spine (Virtual Meeting)  2020年11月  Tokyo Metropolitan Neurological Hospital

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:Tokyo  

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  • 脊椎脊髄診療経験に乏しい脳神経外科における脊椎脊髄診療の立ち上げ

    佐々田晋、安原隆雄、水田 亮、木村 颯、小川智之、久壽米木亮、高橋雄一、小林和樹

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 脊椎手術後のパーキンソン病患者の術後転帰の予測因子

    馬越通有、安原隆雄、佐々木達也、村井 智、河内 哲、藪野 諭、伊達 勲

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 大学病院脳神経外科脊椎脊髄外科医の臨床・教育・研究・学会・私生活

    安原隆雄、馬越通有、河内 哲、藪野 諭、菅原千明、伊達 勲

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 脊髄悪性神経膠腫の治療

    藪野 諭、安原隆雄、亀田雅博、菅原千明、河内 哲、冨田陽介、馬越通有、伊達 勲

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 当科における脊髄硬膜・硬膜外動静脈瘻の治療戦略

    河内 哲、安原隆雄、平松匡文、馬越通有、冨田陽介、藪野 諭、亀田雅博、菱川朋人、杉生憲志、伊達 勲

    第35回日本脊髄外科学会(Web開催)  2020年11月  東京都立神経病院 脳神経外科

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    開催年月日: 2020年11月9日 - 2020年11月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 小児脳室内・脳室近傍腫瘍による閉塞性水頭症に対する第3脳室底開窓術の長期成績─成人症例との比較から─(シンポジウム)

    亀田雅博、黒住和彦、藤井謙太郎、島津洋介、石田穣治、安原隆雄、市川智継、小野成紀、伊達 勲

    第27回一般社団法人日本神経内視鏡学会(現地・Web併催)  2020年11月  和歌山県立医科大学 脳神経外科

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    開催年月日: 2020年11月5日 - 2020年11月6日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:和歌山  

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  • 脊椎脊髄悪性リンパ腫の4例

    駿河和城、安原隆雄、河内 哲、馬越通有、冨田陽介、藪野 諭、亀田雅博、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 80歳以上の超高齢者脊椎脊髄症例に対する手術─周術期の問題点と周術期管理センターの有用性─

    安原隆雄、馬越通有、菱川朋人、亀田雅博、藤井謙太郎、平松匡文、島津洋介、佐々木達也、春間 純、森松博史、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • クリーブランドクリニック脳神経外科─臨床リサーチフェローの生活─(シンポジウム) 招待

    堀 佑輔、安原隆雄、菱川朋人、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:岡山  

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  • 脳梗塞モデルラットに対するカプセル化SB623脳内移植による治療効果の検討

    河内 哲、安原隆雄、亀田雅博、馬越通有、冨田陽介、藪野 諭、菅原千明、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • ラット中大脳動脈閉塞モデルにおけるcrossed cerebellar diaschisis 小脳血流と遺伝子発現解析

    木谷尚哉、杉生憲志、菱川朋人、安原隆雄、平松匡文、西廣真吾、高橋 悠、村井 智、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 脊椎脊髄腹臥位手術における整容面の工夫

    菅原千明、安原隆雄、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 脊髄悪性神経膠腫の治療

    藪野 諭、安原隆雄、亀田雅博、菅原千明、河内 哲、冨田陽介、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 当院における小児のてんかん外科手術51症例の治療成績と精神発達の変化の検討

    岡崎洋介、佐々木達也、細本 翔、亀田雅博、安原隆雄、上利 崇、秋山倫之、小林勝弘、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

     詳細を見る

    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 迷走神経求心路刺激・遠心路刺激のパーキンソン病モデルラットに対する有効性

    細本 翔、佐々木達也、金 一徹、桑原 研、岡崎洋介、藪野 諭、河内 哲、冨田陽介、馬越通有、亀田雅博、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 未破裂脳動脈瘤開頭術後慢性硬膜下血腫発生と脳萎縮の関連性の検証

    山岡陽子、土方保和、安原隆雄、杉生憲志、菱川朋人、平松匡文、春間 純、高橋 悠、村井 智、西 和彦、佐藤 悠、胡谷侑貴、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 徐波睡眠期持続性棘徐波をもつてんかん(CSWS)に対する脳梁離断術の有用性

    外間まどか、佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、秋山倫之、小林勝之、伊達 勲

    (一社)日本脳神経外科学会第79回学術総会(現地・Web併催)  2020年10月  岡山大学大学院医歯薬学総合研究科 脳神経外科

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    開催年月日: 2020年10月15日 - 2020年10月17日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:岡山  

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  • 頚椎症性脊髄症に対する治療戦略─椎弓形成術者の立場から─(主題) 招待

    安原隆雄、馬越通有、伊達 勲

    第27回日本脊椎・脊髄神経手術手技学会学術集会(Web開催)  2020年10月  亀田総合病院 脊椎脊髄外科

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    開催年月日: 2020年10月2日 - 2020年10月3日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:千葉  

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  • 岡山県における脳脊髄動静脈シャント疾患の悉皆調査(シンポジウム)

    村井 智、平松匡文、石橋良太、高井洋樹、鈴木越治、山岡陽子、西 和彦、高橋 悠、菱川朋人、安原隆雄、杉生憲志、伊達 勲

    第49回日本脳卒中の外科学会学術集会:STROKE 2020(Web開催)  2020年8月  奈良県立医科大学 脳神経外科

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    開催年月日: 2020年8月23日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:横浜  

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  • 脳虚血に対する基礎研究─我々の経験と今後の展望─

    安原隆雄、亀田雅博、河内 哲、藪野 諭、菱川朋人、平松匡文、西廣真吾、黒住和彦、杉生憲志、伊達 勲

    第45回日本脳卒中学会学術集会:STROKE 2020(Web開催)  2020年8月  杏林大学 脳神経外科

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    開催年月日: 2020年8月23日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 岡山県における脊椎脊髄動静脈シャント疾患の悉皆調査

    平松匡文、石橋良太、高井洋樹、村井 智、鈴木越治、宮崎裕子、高橋 悠、木谷尚哉、菱川朋人、安原隆雄、杉生憲志、伊達 勲

    第49回日本脳卒中の外科学会学術集会:STROKE 2020(Web開催)  2020年8月  奈良県立医科大学 脳神経外科

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    開催年月日: 2020年8月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • Fusion画像を用いた頭蓋内・脊髄動静脈瘻の直達術前シミュレーション

    平松匡文、菱川朋人、安原隆雄、高橋 悠、村井 智、西 和彦、山岡陽子、杉生憲志、伊達 勲

    第49回日本脳卒中の外科学会学術集会:STROKE 2020(Web開催)  2020年8月  奈良県立医科大学 脳神経外科

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    開催年月日: 2020年8月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • Safety and clinical outcomes in traumatic brain injury patients: Interim analysis of the STEMTRA trail in the Asian subpopulation

    Yasuhara T, Sasaki T, Okonkwo DO, Kawabori S, Imai H, Suenaga J, Nakamura H, Karasawa Y, Kaneko T, Bates D

    2019 World Federation of Neurosurgical Societies (2019 WFNS)  2019年9月 

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    開催年月日: 2019年9月9日 - 2019年9月12日

    記述言語:英語   会議種別:口頭発表(一般)  

    開催地:Beijing  

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  • 中枢神経系疾患に対する細胞療法─基礎研究を行ってきた移植グループが国際共同研究に参加した経験─

    安原隆雄、亀田雅博、佐々木達也、守本 純、金 恭平、馬越通有、冨田陽介、河内 哲、藪野 諭、金 一徹、桑原 研、細本 翔、岡崎洋介、伊達 勲

    第20回日本分子脳神経外科学会  2019年8月  東京大学医学部 脳神経外科

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    開催年月日: 2019年8月9日 - 2019年8月10日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 岡山大学における脳深部刺激療法の入院・外来における他職種・他診療科連携と課題

    佐々木達也、細本 翔、桑原 研、金 一徹、亀田雅博、安原隆雄、伊達 勲

    第22回日本臨床脳神経外科学会  2019年7月  岡山旭東病院

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    開催年月日: 2019年7月20日 - 2019年7月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 大学病院脳神経外科と地域医療の連携

    安原隆雄、菱川朋人、亀田雅博、黒住和彦、藤井謙太郎、平松匡文、佐々木達也、杉生憲志、伊達 勲

    第22回日本臨床脳神経外科学会  2019年7月  岡山旭東病院

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    開催年月日: 2019年7月20日 - 2019年7月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 脳脊髄血管外科におけるfusion imageの有用性(シンポジウム)

    菱川朋人、平松匡文、安原隆雄、杉生憲志、伊達 勲

    第22回日本臨床脳神経外科学会  2019年7月  岡山旭東病院

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    開催年月日: 2019年7月20日 - 2019年7月21日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:岡山  

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  • ラット中大脳動脈閉塞モデルにおけるcrossed cerebellar diaschisis

    木谷尚哉、杉生憲志、菱川朋人、安原隆雄、平松匡文、高橋 悠、村井 智、伊達 勲

    脳循環代謝サマーキャンプ2019  2019年7月  東北大学大学院医学系研究科 神経外科学分野

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    開催年月日: 2019年7月13日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:仙台  

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  • 頭蓋頚椎移行部腫瘍に対する治療戦略─5年間の自験例を振り返って─

    安原隆雄、菱川朋人、黒住和彦、亀田雅博、藤井謙太郎、平松匡文、佐々木達也、伊達 勲

    第31回日本頭蓋底外科学会  2019年7月  神戸大学大学院医学研究科 脳神経外科

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    開催年月日: 2019年7月11日 - 2019年7月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:神戸  

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  • トルコ鞍部・近傍病変に対する磁場式ナビゲーション併用高解像度鏡視下手術

    黒住和彦、亀田雅博、藤井謙太郎、冨田祐介、安原隆雄、伊達 勲

    第31回日本頭蓋底外科学会  2019年7月  神戸大学大学院医学研究科 脳神経外科

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    開催年月日: 2019年7月11日 - 2019年7月12日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:神戸  

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  • Crossed cerebellar diaschisis following transient middle cerebral artery occlusion in rats

    Kidani N, Sugiu K, Hishikawa T, Yasuhara T, Hiramatsu M, Date I

    The 29th International Symposium on Cerebral Blood Flow, Metabolism and Function & The 14th International Conference on Quantification of Brain Function with PET: BRAIN & BRAIN PET 2019  2019年7月 

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    開催年月日: 2019年7月4日 - 2019年7月7日

    記述言語:英語   会議種別:ポスター発表  

    開催地:Yokohama  

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  • 骨粗鬆症性椎体圧迫骨折による遅発性麻痺に対する外科治療

    三好康之、眞鍋博明、安原隆雄、谷口美季、大西 学、目黒俊成、小野成紀

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:札幌  

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  • 胸椎レベルに独立した脊髄空洞症を伴ったC1/2部血管芽腫の1例

    守本 純、安原隆雄、金 恭平、馬越通有、冨田陽介、河内 哲、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:札幌  

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  • 脊髄癒着性くも膜炎に対する治療戦略

    安原隆雄、佐々田晋、守本 純、金 恭平、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:札幌  

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  • キアリ奇形I型の手術におけるデュラウェーブ による硬膜再建の1例

    冨田陽介、安原隆雄、馬越通有、金 恭平、守本 純、亀田雅博、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:札幌  

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  • 片側椎弓切除による開窓で摘出を行った脊髄類皮嚢腫の1例

    馬越通有、安原隆雄、守本 純、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:札幌  

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  • 高度下肢麻痺を呈し小児脊椎Langerhans細胞組織球症が疑われた1例

    河内 哲、安原隆雄、亀田雅博、冨田陽介、馬越通有、金 恭平、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:札幌  

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  • 脊髄癒着性くも膜炎に対する治療戦略

    安原隆雄、佐々田晋、守本 純、金 恭平、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第34回日本脊髄外科学会  2019年6月  医療法人社団研仁会 北海道脳神経外科記念病院

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    開催年月日: 2019年6月20日 - 2019年6月21日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:札幌  

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  • 小児脳腫瘍に対する鏡視下手術(シンポジウム)

    黒住和彦、亀田雅博、藤井謙太郎、冨田祐介、安原隆雄、伊達 勲

    第47回日本小児神経外科学会  2019年6月  新潟大学脳研究所 脳神経外科学分野

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    開催年月日: 2019年6月14日 - 2019年6月15日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:新潟  

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  • 中枢神経系疾患に対する再生医療とリハビリテーション医療の可能性(ランチョンセミナー) 招待

    安原隆雄

    第56回日本リハビリテーション医学会学術集会  2019年6月  兵庫医科大学 リハビリテーション医学教室

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    開催年月日: 2019年6月12日 - 2019年6月16日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:神戸  

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  • 脊椎脊髄手術 事始め─安全確実な脊椎脊髄手術のために─(専攻医向けセミナー) 招待

    安原隆雄、伊達 勲

    第39回日本脳神経外科コングレス総会  2019年5月  山形大学医学部 脳神経外科

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    開催年月日: 2019年5月16日 - 2019年5月19日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:横浜  

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  • Novo TTF-A100(オプチューン)による膠芽腫治療時におけるウィッグ作成の試み

    藤井謙太郎、黒住和彦、安原隆雄、冨田祐介、伊達 勲、山岡純三

    第12回日本整容脳神経外科学会  2019年4月  岡山大学大学院 脳神経外科

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    開催年月日: 2019年4月12日 - 2019年4月13日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 頭蓋固定プレート・人工骨に関する合併症全国実態調査(合同シンポジウム) 招待

    安原隆雄、三國信啓、宮本 享、伊達 勲

    第28回脳神経外科手術と機器学会・第12回日本整容脳神経外科学会  2019年4月  岡山大学大学院 脳神経外科

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    開催年月日: 2019年4月12日 - 2019年4月13日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:岡山  

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  • Full HD/4K/8Kシステムを用いた高解像度鏡視下手術(シンポジウム)

    黒住和彦、亀田雅博、藤井謙太郎、冨田祐介、安原隆雄、伊達 勲

    第28回脳神経外科手術と機器学会  2019年4月  岡山大学大学院 脳神経外科

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    開催年月日: 2019年4月12日 - 2019年4月13日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:岡山  

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  • 3Dデータを用いた手術シミュレーション

    守本 純、安原隆雄、伊達 勲

    第28回脳神経外科手術と機器学会  2019年4月  岡山大学大学院 脳神経外科

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    開催年月日: 2019年4月12日 - 2019年4月13日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 難治性てんかんにおける頭蓋内電極留置と焦点切除の2段階手術を安全かつ整容にも配慮して行っている工夫(シンポジウム)

    佐々木達也、細本 翔、桑原 研、金 一徹、柴田 敬、亀田雅博、安原隆雄、小林勝弘、伊達 勲

    第28回脳神経外科手術と機器学会  2019年4月  岡山大学大学院 脳神経外科

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    開催年月日: 2019年4月12日 - 2019年4月13日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:岡山  

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  • ラット中大脳動脈瘤モデルにおけるcrossed cerebellar diaschisis

    木谷尚哉、杉生憲志、菱川朋人、安原隆雄、平松匡文、高橋 悠、村井 智、伊達 勲

    第44回日本脳卒中学会学術集会:STROKE 2019  2019年3月  東京女子医科大学 脳神経内科

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    開催年月日: 2019年3月21日 - 2019年3月23日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 直達術で治療を行った脊髄円錐下方の動静脈瘻の1例

    西 和彦、平松匡文、安原隆雄、杉生憲志、菱川朋人、木谷尚哉、高橋 悠、村井 智、伊達 勲

    第44回日本脳卒中学会学術集会:STROKE 2019  2019年3月  東京女子医科大学 脳神経内科

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    開催年月日: 2019年3月21日 - 2019年3月23日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:横浜  

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  • 慢性期頭部外傷患者に対する細胞移植治療の治験参加経験(シンポジウム)

    安原隆雄、亀田雅博、佐々木達也、守本 純、金 恭平、馬越通有、冨田陽介、河内 哲、金 一徹、桑原 研、細本 翔、伊達 勲

    第42回日本脳神経外傷学会  2019年3月  神戸大学大学院医学研究科 脳神経外科

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    開催年月日: 2019年3月8日 - 2019年3月9日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:淡路  

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  • 頭蓋頚椎以降部動静脈瘻の直達術における3D fusion画像を用いた術前シミュレーション

    西 和彦、平松匡文、安原隆雄、守本 純、杉生憲志、菱川朋人、木谷尚哉、高橋 悠、村井 智、伊達 勲

    第42回日本脳神経CI学会総会  2019年3月  日本医科大学 脳神経外科

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    開催年月日: 2019年3月1日 - 2019年3月2日

    記述言語:日本語   会議種別:ポスター発表  

    開催地:東京  

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  • 脳神経外科領域の指定難病 招待

    安原隆雄

    第2回岡山県難病診療連携拠点病院研修会  2019年2月  岡山県難病診療連携拠点病院研修会(岡大学病院)・岡山県

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    開催年月日: 2019年2月25日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:岡山  

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  • トルコ鞍部・近傍病変における高解像度鏡視下手術

    黒住和彦、亀田雅博、藤井謙太郎、冨田祐介、安原隆雄、伊達 勲

    第29回日本間脳下垂体腫瘍学会  2019年2月  大阪大学大学院医学系研究科 脳神経機能再生学

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    開催年月日: 2019年2月22日 - 2019年2月23日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 下垂体腺腫に対する経蝶形骨洞手術後の低Na血症についての検討(シンポジウム)

    冨田祐介、黒住和彦、稲垣兼一、亀田雅博、安原隆雄、市川智継、大塚文男、伊達 勲

    第29回日本間脳下垂体腫瘍学会  2019年2月  大阪大学大学院医学系研究科 脳神経機能再生学

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    開催年月日: 2019年2月22日 - 2019年2月23日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:大阪  

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  • 下垂体腺腫に対する経蝶形骨洞手術後の低Na血症についての検討

    冨田祐介、黒住和彦、稲垣兼一、亀田雅博、安原隆雄、市川智継、大塚文男、伊達 勲

    第85回岡山内分泌同好会  2019年2月 

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    開催年月日: 2019年2月20日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 8歳MRI陰性側頭葉てんかんの1手術例

    佐々木達也、井本良二、松田奈央子、柴田 敬、秋山麻里、亀田雅博、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第13回日本てんかん学会中国・四国地方会  2019年2月  山口県立総合医療センター 脳神経外科・てんかんセンター

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    開催年月日: 2019年2月16日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:下関  

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  • 脊髄血管奇形の新知見─脊髄硬膜・硬膜外動静脈瘻と脳神経外科救急─(指定) 招待

    安原隆雄、平松匡文、菱川朋人、守本 純、杉生憲志、伊達 勲

    第24回日本脳神経外科救急学会  2019年2月  関西医科大学総合医療センター 脳神経外科

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    開催年月日: 2019年2月1日 - 2019年2月2日

    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:大阪  

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  • パーキンソン病モデルラットに対する脊髄電気刺激療法

    桑原 研、佐々木達也、細本 翔、金 一徹、岡崎三保子、河内 哲、冨田陽介、馬越通有、金 恭平、守本 純、亀田雅博、安原隆雄、伊達 勲

    第58回日本定位・機能神経外科学会  2019年1月  東京都立神経病院 脳神経外科

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    開催年月日: 2019年1月25日 - 2019年1月26日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 両側GPi-DBSが著効した壮年期発症のDYT1陽性全身性ジストニアの1例(シンポジウム)

    金 一徹、佐々木達也、岡崎三保子、桑原 研、細本 翔、亀田雅博、安原隆雄、伊達 勲

    第58回日本定位・機能神経外科学会  2019年1月  東京都立神経病院 脳神経外科

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    開催年月日: 2019年1月25日 - 2019年1月26日

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:東京  

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  • 定位脳手術における技術継承のための重要点─手術マネジメントの初期経験を振り返って─

    佐々木達也、細本 翔、岡崎三保子、金 一徹、桑原 研、亀田雅博、安原隆雄、伊達 勲

    第58回日本定位・機能神経外科学会  2019年1月  東京都立神経病院 脳神経外科

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    開催年月日: 2019年1月25日 - 2019年1月26日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • SISCOMが有用であったMRI陰性の内側前頭葉てんかんの1手術例

    細本 翔、佐々木達也、桑原 研、金 一徹、岡崎三保子、柴田 敬、亀田雅博、安原隆雄、上利 崇、秋山麻里、小林勝弘、伊達 勲

    第42回日本てんかん外科学会  2019年1月  新潟大学脳研究所 脳神経外科学

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    開催年月日: 2019年1月24日 - 2019年1月25日

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 当院でのNovo TTF-100A(オプチューン)治療における整容面に配慮し多職種間の連携

    島津洋介、藤井謙太郎、黒住和彦、安原隆雄、竹内加恵、小銭知代、山岡純三、伊達 勲

    第29回脳神経外科手術と機器学会  2020年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜(Web併催)  

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  • てんかん外科手術における慢性頭蓋内電極留置を安全、確実に行うための工夫

    佐々木達也、細本 翔、岡崎洋介、亀田雅博、安原隆雄、伊達 勲

    第29回脳神経外科手術と機器学会  2020年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜(Web併催)  

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  • フルHD・4K・8Kシステムによる内視鏡下経鼻的経蝶形骨洞手術(シンポジウム)

    黒住和彦、亀田雅博、藤井謙太郎、島津洋介、坪井伸成、安原隆雄、伊達 勲

    第29回脳神経外科手術と機器学会  2020年9月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:横浜(Web併催)  

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  • 80歳以上の高齢者脊椎症例に対する手術─周術期の問題点と周術期管理センターの有用性─(シンポジウム)

    安原隆雄、馬越通有、菱川朋人、黒住和彦、亀田雅博、藤井謙太郎、平松匡文、島津洋介、佐々木達也、春間 純、伊達 勲

    第33回日本老年脳神経外科学会  2020年7月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:倉敷(誌上開催)  

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  • 巨大小脳動静脈奇形に対する経動脈塞栓術により合併した脊髄空洞症の改善を認めた1例

    川上真人、平松匡文、安原隆雄、杉生憲志、菱川朋人、高橋 悠、村井 智、西 和彦、山岡陽子、伊達 勲

    第89回(一社)日本脳神経外科学会中国四国支部学術集会(Web開催)  2020年4月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:高松  

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  • 集中治療室管理を要した重症頭部外傷症例の長期予後(シンポジウム)

    安原隆雄、湯本哲也、村井 智、中尾篤典、伊達 勲

    第43回日本脳神経外傷学会  2020年3月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:箱根(誌上開催)  

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  • 運動野近傍に存在するFocal cortical dysplasia (bottom of sulcus)の1手術例

    佐々木達也、金 聖泰、岡崎洋介、細本 翔、亀田雅博、安原隆雄、小林勝弘、伊達 勲

    第14回日本てんかん学会中国・四国地方会  2020年2月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:米子  

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  • 薬剤抵抗性てんかんにおける頭蓋内電極留置術を安全かつ整容にも配慮して行っている最近の工夫

    佐々木達也、細本 翔、岡崎洋介、亀田雅博、安原隆雄、花岡義行、秋山倫之、小林勝弘、伊達 勲

    第7回全国てんかんセンター協議会 広島大会  2020年2月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:広島  

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  • 経鼻的経蝶形骨洞手術におけるフルHDと4K/8K内視鏡との比較

    黒住和彦、亀田雅博、藤井謙太郎、島津洋介、冨田祐介、坪井伸成、安原隆雄、伊達 勲

    第30回日本間脳下垂体腫瘍学会  2020年2月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:東京  

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  • 当院における新皮質てんかんの外科治療の検討

    佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第43回日本てんかん外科学会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:浜松  

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  • 島回を発作焦点とするMRI陰性てんかんで再手術を要した1例

    細本 翔、佐々木達也、兵頭勇紀、亀田雅博、安原隆雄、秋山麻里、秋山倫之、小林勝弘、伊達 勲

    第43回日本てんかん外科学会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:浜松  

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  • 脳深部刺激療法の入院・外来における他職種・他診療科連携と課題

    佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、伊達 勲

    第59回日本定位・機能神経外科学会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:浜松  

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  • 当院における小児のてんかん外科手術の治療成績

    岡崎洋介、佐々木達也、細本 翔、桑原 研、金 一徹、亀田雅博、安原隆雄、秋山麻里、小林勝弘、伊達 勲

    第43回日本てんかん外科学会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:浜松  

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  • 頭蓋頚椎移行部腫瘍の画像診断と治療

    安原隆雄、菱川朋人、黒住和彦、亀田雅博、藤井謙太郎、平松匡文、佐々木達也、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 鏡視下手術とナビゲーション・高解像度モニター(シンポジウム)

    黒住和彦、亀田雅博、安原隆雄、菱川朋人、佐々木達也、島津洋介、冨田祐介、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:岡山  

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  • 3DDSA-MRI fusion画像を用いた脊髄動静脈瘻の術前診断(シンポジウム)

    平松匡文、安原隆雄、杉生憲志、菱川朋人、春間 純、高橋 悠、村井 智、西 和彦、山岡陽子、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:岡山  

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  • 最近経験した珍しい小児脊椎脊髄腫瘍の画像診断と治療

    安原隆雄、守本 純、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • 本態性振戦患者に対する定位視床手術におけるファイバートラクトグラフィーの有用性

    岡崎洋介、佐々田晋、佐々木達也、細本 翔、桑原 研、金 一徹、亀田雅博、上利 崇、安原隆雄、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • トルコ鞍部・近傍病変に対する磁場式ナビゲーション併用高解像度鏡視下手術

    島津洋介、黒住和彦、亀田雅博、藤井謙太郎、安原隆雄、伊達 勲

    第43回日本脳神経CI学会総会  2020年1月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:岡山  

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  • Perimedullary AVFとepidural AVFを合併した1例

    平松匡文、安原隆雄、杉生憲志、伊達 勲

    第8回Interventional Anatomy in Neurovascular System (IANS) Seminar  2019年12月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:福岡  

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  • てんかん手術における確実な焦点切除と脳機能温存を両立させる工夫

    佐々木達也、岡崎洋介、細本 翔、亀田雅博、安原隆雄、伊達 勲

    第24回関西脳神経外科手術研究会  2019年12月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 中枢神経系疾患に対する再生医療とリハビリテーション医療の可能性 招待

    安原隆雄、伊達 勲

    2019年岡山県理学療法卒後研修会  2019年11月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

    開催地:岡山  

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  • 下垂体腺腫に対する経蝶形骨洞手術後の遅発性低Na血症についての検討

    冨田祐介、黒住和彦、坪井伸成、稲垣兼一、亀田雅博、安原隆雄、市川智継、大塚文男、伊達 勲

    第26回一般社団法人日本神経内視鏡学会  2019年11月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • 高解像度3D外視鏡を用いた当院での手術経験

    藤井謙太郎、黒住和彦、島津洋介、冨田祐介、亀田雅博、菱川朋人、安原隆雄、佐々木達也、伊達 勲

    第26回一般社団法人日本神経内視鏡学会  2019年11月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:横浜  

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  • Cervical spondylotic myelopathy - anterior versus posterior cervical laminoplasty: Opinion from a posterior dominant surgeon (Lunchon Seminar) 招待

    Yasuhara T, Date I

    2019 Congress of Neurological Surgeons Annual Meeting: CNS2019  2019年10月 

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    記述言語:英語   会議種別:口頭発表(基調)  

    開催地:San Francisco  

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  • Significance of pre-operative angiographic diagnosis in cases of spinal dural and epidural arteriovenous fistula

    Nishi K, Hiramatsu M, Sugiu K, Yasuhara T, Hishikawa T, Kidani N, Takahashi Y, Murai S, Date I

    15th Congress of The World Federation of Interventional and Therapeutic Neuroradiology  2019年10月 

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    記述言語:英語  

    開催地:Naples  

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  • 中枢神経系領域における再生医療─脳神経外科での基礎と臨床における研究の現状と展望─

    安原隆雄、亀田雅博、佐々木達也、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:大阪  

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  • 岡山大学てんかんセンターにおける新皮質てんかんの外科治療の検討

    佐々木達也、岡崎洋介、細本 翔、金 一徹、桑原 研、亀田雅博、安原隆雄、秋山倫之、小林勝弘、伊達 勲

    第53回日本てんかん学会学術集会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:神戸  

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  • 新皮質てんかん38例に対する外科治療成績の検討

    佐々木達也、岡崎洋介、細本 翔、金 一徹、桑原 研、亀田雅博、安原隆雄、秋山倫之、小林勝弘)、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • 当院での高解像度3D外視鏡システムによるheads up surgeryの経験

    藤井謙太郎、黒住和彦、冨田祐介、亀田雅博、菱川朋人、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • パーキンソン病モデルラットに対する迷走神経刺激療法の有効性

    金 一徹、佐々木達也、岡崎洋介、細本 翔、桑原 研、藪野 諭、河内 哲、冨田陽介、馬越通有、亀田雅博、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • Parkinson病に伴う脊椎疾患に対する外科治療─術後2年の治療成績─

    馬越通有、安原隆雄、佐々木達也、村井 智、冨田陽介、河内 哲、藪野 諭、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 脊髄症状を呈した悪性リンパ腫の3例

    河内 哲、安原隆雄、馬越通有、冨田陽介、藪野 諭、亀田雅博、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • パーキンソン病モデルに対する持続脊髄電気刺激療法の有用性

    桑原 研、佐々木達也、岡崎洋介、細本 翔、金 一徹、藪野 諭、河内 哲、冨田陽介、馬越通有、亀田雅博、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • 当科における脊髄癒着性くも膜炎に対する治療

    藪野 諭、安原隆雄、亀田雅博、河内 哲、冨田陽介、馬越通有、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • 当院における小児てんかん42症例に対する外科手術の治療成績

    岡崎洋介、佐々木達也、細本 翔、桑原 研、金 一徹、亀田雅博、安原隆雄、秋山麻里、秋山倫之、小林勝弘、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • 高度の浮腫を伴った頭蓋頚椎移行部血管芽腫に対して摘出術を施行した2症例の手術の工夫と術後経過についての検討

    菅原千明、安原隆雄、佐々木達也、平松匡文、藤井謙太郎、亀田雅博、菱川朋人、黒住和彦、杉生憲志、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • Cyanotic congenital heart diseaseに合併した小児頭蓋内膿瘍の検討

    胡谷侑貴、佐々木達也、亀田雅博、安原隆雄、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:大阪  

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  • 側頭葉てんかん手術における術中運動誘発電位モニタリングの有用性

    細本 翔、佐々木達也、大西功真、黒川友里、岡崎洋介、金 一徹、桑原 研、亀田雅博、安原隆雄、上利 崇、伊達 勲

    (一社)日本脳神経外科学会第78回学術総会  2019年10月 

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    記述言語:日本語   会議種別:ポスター発表  

    開催地:大阪  

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  • Microscopic spinal surgeries, MIS-PLIF with percutaneous pedicle scerw insertion 招待

    Yasuhara T, Date I

    4th International Society of Minimally Invasive Neurosurgery (ISMINS): Minimizing Surgeries and Maximizing Outcomes in Neurosurgery  2019年10月 

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    記述言語:英語   会議種別:口頭発表(招待・特別)  

    開催地:Phuket  

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  • Full HD/4K/8K内視鏡による経蝶形骨洞手術(シンポジウム)

    黒住和彦、亀田雅博、藤井謙太郎、冨田祐介、安原隆雄、伊達 勲

    第24回日本脳腫瘍の外科学会  2019年9月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(公募)  

    開催地:浜松  

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  • キアリ奇形および関連病態に対する最近の手術(主題)

    安原隆雄、佐々田晋、豊嶋敦彦、守本 純、金 恭平、馬越通有、冨田陽介、河内 哲、藪野 諭、伊達 勲

    第26回日本脊椎・脊髄神経手術手技学会  2019年9月 

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    記述言語:日本語   会議種別:口頭発表(基調)  

    開催地:大阪  

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  • 膠芽腫に対するNovo TTF-A100(オプチューン)治療におけるウィッグ作製の試み

    黒住和彦、藤井謙太郎、安原隆雄、冨田祐介、山岡純三、伊達 勲

    第24回日本脳腫瘍の外科学会  2019年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:広島  

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  • Slab MIPとfusion画像を用いた脊髄シャント疾患の診断と治療(特別講演) 招待

    平松匡文、安原隆雄、杉生憲志

    第4回Dural Shunt and Anatomy道場 Japan  2019年4月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

    開催地:東京  

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  • 難治性うつ病モデルラットへのカプセル化間葉系幹細胞移植による脳内微小環境の変化

    金 恭平、安原隆雄、亀田雅博、河内 哲、細本 翔、冨田陽介、馬越通有、木谷尚哉、桑原 研、金 一徹、佐々木達也、伊達 勲

    第18回日本再生医療学会総会  2019年3月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:神戸  

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▼全件表示

受賞

  • てんかん治療研究振興財団研究助成

    2011年  

  • 日本損害保険協会研究助成、かなえ医薬振興財団研究助成

    2010年  

  • 山陽放送学術文化財団研究助成

    2008年  

  • 岡山医学会賞(新見賞)

    2006年6月   岡山医学会  

    安原隆雄

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    受賞区分:国内学会・会議・シンポジウム等の賞  受賞国:日本国

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  • 学会奨励賞

    2005年10月   日本脳神経外科学会  

    安原隆雄

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    受賞区分:国内学会・会議・シンポジウム等の賞  受賞国:日本国

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  • 平成17年度 海外留学助成リサーチフェローシップ

    2005年1月   上原記念生命科学財団  

    安原隆雄

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    受賞区分:出版社・新聞社・財団等の賞  受賞国:日本国

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共同研究・競争的資金等の研究

  • 新生仔低酸素虚血性白質障害に対する細胞移植と運動刺激による機能再建の解析

    研究課題/領域番号:21K11222  2021年04月 - 2024年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    田尻 直輝, 飛田 秀樹, 安原 隆雄

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 神経系に元来備わる自己修復能の活性化法:電気刺激療法を用いて

    研究課題/領域番号:20K09390  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    亀田 雅博, 安原 隆雄, 田尻 直輝, 佐々木 達也

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

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  • 浸潤性脳腫瘍に対する分子標的薬と遺伝子治療との併用療法とその腫瘍微小環境の解明

    研究課題/領域番号:20K09325  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    黒住 和彦, 藤井 謙太郎, 安原 隆雄, 島津 洋介

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • カプセル化細胞移植で細胞治療のメカニズムに迫る:脳梗塞後うつ症状への応用

    研究課題/領域番号:19K09528  2019年04月 - 2022年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    安原 隆雄, 黒住 和彦, 亀田 雅博, 菱川 朋人, 佐々木 達也

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究はヒト間葉系幹細胞由来多能性幹細胞 (hMPSC: human-derived multipotent stem cell) を脳内移植することにより、一過性中大脳動脈閉塞による脳梗塞モデルラットがどのような治療効果をうけるかを示すことである。特にカプセル化細胞移植と直接移植の治療効果の差異を示すことや心理学的な効果を調べることが研究の特徴である。
    研究実績として、2019年度に行う予定であった研究を行うことができたと評価できる。
    脳梗塞モデル作製はおよそ70%の確率で安定して実験に供することができるレベルである。直接細胞移植およびカプセル化細胞移植についても手技は安定した。生体内で移植細胞は少数ながら、1週間後に生存細胞を認めたが、多くは生着しなかった。一方で、カプセル化細胞移植では2週間後にも生存細胞を多数認め、直接細胞移植よりも長期間生存することは明らかであった。脳梗塞モデルにおける脳血流評価を行い論文化した(Nishihiro S, et al. Neuromolecular Med 2019)。運動機能と梗塞巣体積については、移植群において、対照群より改善が得られたが、これまでのところ、カプセル化細胞移植群で、より高い治療効果が得られている。うつ様症状についても行動学的評価を行っているが、関連先行研究として、うつ病モデルラットに対する薬物治療と神経新生について研究をまとめた。(Kin K, et al. Brain Res 2019)。研究の進捗は順調であり、2020年度も予定通りの研究成果を報告できる見込みである。

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  • 頭部外傷うつ病モデルラットに対する細胞移植と運動刺激の併用療法の検討

    研究課題/領域番号:18K10731  2018年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    田尻 直輝, 飛田 秀樹, 森信 繁, 安原 隆雄, 亀田 雅博

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    研究実施計画では、頭部外傷うつ病動物モデルラットを用いて、細胞移植及びリハビリの有する神経・血管新生作用と神経保護・修復作用について研究する予定であった。しかし、所属先が異動となったため、頭部外傷うつ病モデルラットの作成が困難となり、その代案として、研究のコンセプトは変更せずに、社会的ニーズが高い新生児低酸素虚血性白質障害(NWMI)を用いた細胞移植とリハビリ研究に取り組んでいる。
    NWMIは、早産児において分娩時の低酸素虚血が原因でおこる白質障害である。これは脳室周囲白質軟化症(PVL)の一種であるが、脳室周囲にcyst(嚢胞)を伴う重症型のcystic PVLとは異なり、MRIでもcystが認められない軽症型の白質障害である。周産期医療の進歩により、重症型のcystic PVLは激減する一方で、このような軽症型の白質障害は増加傾向にあり、社会問題となっている。
    NWMIは、在胎28-32週の早産児に好発し、症状としては、脳性麻痺を含む運動障害や注意欠陥多動性障害(ADHD)といった認知障害などを引き起こすことが知られている。病理組織学的には、オリゴデンドロサイト後期前駆細胞(preOL)の選択的障害が特徴で、ニューロンの障害は認められない。胎児脳におけるオリゴデンドロサイトの分化段階で、preOLは低酸素虚血による障害を受けやすい。この時に分娩となった新生児は、白質障害のリスクが高まることが報告されており、根本的な治療法は未だに確立されていない。
    本研究では、この疾患モデル動物を用いて、外部からオリゴデンドロサイト前駆細胞(OPC)を補充することで、NWMIの病態や機能改善に繋がるかどうかを検討している(実験1)。また、発育期のリハビリによる効果が期待されるが、豊かな環境で飼育し、成熟後の運動機能の改善効果とその作用機序についても解析を行っている。

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  • 悪性脳腫瘍に対する分子標的薬と遺伝子治療併用の新展開

    研究課題/領域番号:17K10865  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    黒住 和彦, 市川 智継, 安原 隆雄, 藤井 謙太郎

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    グリオーマは脳に発生する悪性腫瘍で原発性脳腫瘍の約30%を占め、悪性グリオーマの予後は極めて不良である。本研究は分子標的薬と遺伝子治療との併用について検討した。分子標的薬bevacizumab、cilengitide、PD-1阻害剤や腫瘍溶解ウイルス、Ad-SGE-REICなどについて、本研究のセットアップを行った。腫瘍はヒト脳腫瘍細胞株や脳腫瘍患者から承諾を得て採取した腫瘍由来細胞を用いて、脳腫瘍マウスモデルを作製した。併用療法について検討、解析中であり、microarrayをおこない、pathway 解析を行っている。統計学的データ解析を行い、学会発表・論文投稿する。

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  • 生体脳に元来備わる神経再生機構の活性化法:電気刺激を用いて

    研究課題/領域番号:17K10828  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    亀田 雅博, 安原 隆雄, 田尻 直輝, 佐々木 達也

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    我々は, 健常なマウスに対して, 電気刺激を与えることで,神経新生が促進させることをすでに確認している。これを受けて,本研究では,中枢神経系疾患に対して電気刺激療法を行い,内因性の神経幹細胞を活性化させることで,脳が元来備え持つ組織修復作用を効果的に誘導できるか検証した.その結果,成体ラットを用いた慢性低灌流モデルに対して,高頻度刺激さらにはlong-term potentiationを誘発させることで神経新生が促進されることで,虚血負荷(慢性低灌流)後の生体がもつ組織修復作用を,効率的に誘導させうることが確認できた。そして,本研究の成果を英文誌上に発表した。

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  • 中枢神経系疾患における神経新生とうつ症状:細胞移植、電気刺激、リハビリによる治療

    研究課題/領域番号:17H04303  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    伊達 勲, 黒住 和彦, 道上 宏之, 藤井 謙太郎, 安原 隆雄, 亀田 雅博, 菱川 朋人, 田尻 直輝, 市川 智継

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    配分額:17030000円 ( 直接経費:13100000円 、 間接経費:3930000円 )

    動物実験において、うつ様行動の程度は神経新生の程度が大きいものほど軽度であることが示された。一方、細胞移植により、神経新生が増強され、うつ様行動が改善することも示された。小型・埋め込み型・24時間持続刺激可能な電気刺激装置の開発により、動物実験における迷走神経刺激や脊髄硬膜外刺激に代表される電気刺激の治療効果が明らかになった。リハビリテーションによる再生医療への可能性も示された。精神症状や神経新生も中枢神経系疾患における新しい治療ターゲットになる可能性がある。

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  • グリオーマ細胞の形質転換誘導による浸潤抑制と抗腫瘍薬増感療法

    研究課題/領域番号:17K10866  2017年04月 - 2018年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    市川 智継, 黒住 和彦, 安原 隆雄, 亀田 雅博, 藤井 謙太郎

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    悪性グリオーマの治療抵抗性の最大の原因となっている「浸潤性増殖」を克服する、新しい治療法を開発することを目的として本研究を開始した。まず、腫瘍細胞の多様性と表現型シフト(形質転換)を個別に再現する、我々のオリジナルの培養細胞と動物モデルを用いて、浸潤性を規定する遺伝子の探索を行った。本研究の特色と独創的な点は、(1)浸潤能と血管新生能において表現型の異なるペアのオリジナルの培養細胞と動物モデルを用いることと、(2)腫瘍細胞の形質転換誘導によって治療効果を得るという革新的な治療ストラテジーにある。
    これまでの我々の研究結果から、腫瘍細胞におけるannexin A2 遺伝子の発現が血管新生に依存した細胞増殖に関与することを、マイクロアレイ解析の結果をもとに示しているが、本研究においては、まず同様のマイクロアレイの結果をもとに、annexin A2の発現に関連する遺伝子の解析を行った。その結果、fibroblast growth factor 13 (FGF13)遺伝子を、浸潤性を増強する遺伝子として同定し、更にグリオーマにおける機能的解析も行なうことができた。本研究の成果は誌上発表した。
    つぎに、グリオーマ細胞へのannexin A2 遺伝子導入が「血管新生-浸潤シフト」という形質転換を誘導し、(1)腫瘍細胞の浸潤能抑制、(2)腫瘍細胞の薬剤感受性上昇というふたつの機序により抗腫瘍効果を発揮することを、培養細胞、動物モデルで示すために、annexin A2 遺伝子を持つウィルスベクターを作成した。これを用いて腫瘍細胞への遺伝子導入を行い、基礎的な実験と実験的治療を行った。

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  • 脳梗塞におけるうつ症状と神経新生

    研究課題/領域番号:16K10722  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    安原 隆雄, 市川 智継, 黒住 和彦, 道上 宏之, 亀田 雅博, 上利 崇, 菱川 朋人, 佐々木 達也, 藤井 謙太郎

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    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    うつ病・うつ状態は、現代のストレス社会において大きな問題であり、メカニズムの解明や新しい治療法が望まれる。私たちはうつ病モデルラットを用いた研究で、次のことを明らかにした。1.うつ病様行動を示すWistar Kyoto ratでは、海馬における神経新生が減弱していた。2.うつ病様行動を示すWistar Kyoto ratに対して、側脳室内にカプセル化骨髄幹細胞移植を行うと、うつ病様行動の改善や神経新生の増強が認められた。3.上記2の治療効果のメカニズムは、様々な神経栄養因子や成長因子がカプセル化細胞から分泌されることによると考えられた。

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  • SCSの抗てんかん作用

    研究課題/領域番号:26462209  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    近藤 聡彦, 安原 隆雄, 亀田 雅博, 上利 崇

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    ラットの脊髄刺激(SCS:spinal cord stimulation)による抗てんかん作用の検討のため、上位脊髄の硬膜外に電極を留置し、留置翌日より1日1時間のSCSを1週間継続した。刺激強度は運動誘発閾値の80%に設定し、刺激周波数は2,10,15,25,50,100,200の7種類に設定した。SCSを行った群と対照群のラットの腹腔内にカイニン酸(12mg/kg)を投与して癲癇を誘発し、投与後6時間以内の癲癇発作の重症度を判定した。その結果、いずれの刺激条件でも重症度を抑える傾向にあったが、統計学的には200Hzで刺激した群のみが対照群と比較して有意差を持って抗てんかん作用を示した。

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  • 新規OVと分子標的薬の併用療法

    研究課題/領域番号:26462182  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    黒住 和彦, 伊達 勲, 安原 隆雄

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    本研究では、腫瘍微小環境をターゲットとした分子標的薬と新規腫瘍溶解ウイルス(OV: 34.5ENVE)との併用による治療効果について実験する。現在、本研究のセットアップを行っている。代替実験として、34.5ENVEのプロトタイプとなる抗血管新生作用を持つvasculostatin蛋白を発現するOV:RAMBO (for Rapid Antiangiogenesis Mediated By Oncolytic virus)を使用した、抗浸潤作用の実験を行っており、Bevacizumab誘導性浸潤モデルにてRAMBOを使用することにより抗浸潤効果を得ることができた。

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  • 中枢神経系疾患に対する細胞移植の臨床応用の扉を開く:カプセル化と電気刺激を用いて

    研究課題/領域番号:26293323  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    伊達 勲, 黒住 和彦, 道上 宏之, 近藤 聡彦, 安原 隆雄, 亀田 雅博, 上利 崇, 菱川 朋人

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    配分額:15860000円 ( 直接経費:12200000円 、 間接経費:3660000円 )

    パーキンソン病モデル動物に対する脊髄刺激治療の治療効果を明らかにした。脳梗塞モデル動物に対する経頚動脈的骨髄幹細胞移植治療において、発症から24時間後の移植が高い治療効果を示すことを明らかにした。脳梗塞モデル動物に対する細胞移植と電気刺激治療を組み合わせた研究では、移植細胞の脳梗塞への遊走は電気刺激により増強され、行動学的・組織学的に治療効果も明らかにされた。

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  • Bevacizumab誘導性脳腫瘍浸潤に対する新規治療法の開発

    研究課題/領域番号:26670644  2014年04月 - 2017年03月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    伊達 勲, 黒住 和彦, 杉生 憲志, 安原 隆雄

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    配分額:3770000円 ( 直接経費:2900000円 、 間接経費:870000円 )

    近年悪性神経膠腫に対して抗VEGF抗体(bevacizumab) が用いられるようになり、その治療効果が報告されている。しかし、血管新生抑制により治療効果をもたらす一方で、腫瘍細胞の浸潤が誘発されるともいわれる。我々は、bevacizumab投与により誘発された脳腫瘍の浸潤性変化に対するintegrin阻害剤 (cilengitide) の併用効果について検討した。Bevacizumab、cilengitide併用治療群ではbevacizumab単独治療群と比較し、脳腫瘍浸潤性変化が減少し、浸潤関連因子の発現が抑制された。

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  • 悪性グリオーマにおける血管新生-浸潤シフトの分子生物学的機構の解明

    研究課題/領域番号:25462261  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    市川 智継, 黒住 和彦, 伊達 勲, 安原 隆雄, 亀田 雅博

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    グリオーマの血管新生能と浸潤能を規定するkey moleculeであるannexin A2の発現をコントロールし、その下流で動く遺伝子をマイクロアレイ法により網羅的に解析した。その結果、血管新生非依存性浸潤を規定する遺伝子の候補としてFGF13を抽出し、動物モデルを用いて浸潤と血管新生における機能を検証した。FGF13は細胞骨格を制御することにより浸潤能に関与していると考えられた。

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  • 電気刺激は移植細胞の遊走能を高めるか?: メカニズムに迫り、臨床応用への道を探る

    研究課題/領域番号:25861277  2013年04月 - 2016年03月

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    安原 隆雄

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    脳梗塞モデルラットを作製し、病側大脳皮質硬膜外に電気刺激を、健側大脳皮質内に蛍光標識骨髄幹細胞移植を行った。2週間持続刺激を行い、細胞生存・分化・遊走の変化を確認したところ、患側への遊走が増加していた。生存率・分化能については、有意差が得られなかった。内在性神経幹細胞の変化をみるために、BrdUを用いた増殖細胞のラベルを行ったところ、電気刺激によりBrdU陽性細胞は増幅され、神経前駆細胞数が増加していた。

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  • パーキンソン病、脳梗塞、頭部外傷、てんかんなど中枢神経系疾患モデル動物に対する神経移植再生療法

    2012年11月 - 2014年12月

    岡山大学  若手研究者スタートアップ研究支援事業 

    安原隆雄

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:500000円 ( 直接経費:500000円 )

    パーキンソン病、脳梗塞、頭部外傷、てんかんなど中枢神経系疾患モデル動物に対する神経移植再生療法がメインテーマです。2001年、本学にてパーキンソン病に対するVEGF産生細胞株移植をテーマとして、伊達勲教授の下、研究を開始いたしました。2005年、Medical College of Georgiaに留学させていただき、Human neu r a I stem ce I Iを用いたパーキンソン病に対する移植治療、新生ラット脳虚血に対する細胞療法、サル全脳虚血モデルに対する骨髄幹細胞移植、ラット廃用モデルにおける神経新生の変化、ブルーベリーの脳梗塞に対する治療効果等多岐に渡る研究をさせていただきました。2007年に本学に復帰させていただき、てんかんモデルラットに対する薬物・細胞療法、頭部外傷に対するエリスロポイエチンの治療、脳梗塞モデルに対する電気刺激治療など、多数の研究に携わりました。2010年から2年間新小文字病院脊髄脊椎外科で臨床研修・臨床研究をさせていただき、腰椎多椎間固定における隣接椎間障害や頚椎椎間板ヘルニアの左右差に関する研究等を行っておりました。2012年10月よりまた本学に復帰させていただき、研究を継続する予定です。

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  • BDNF産生細胞株移植のてんかんモデルラットに対する影響 -神経保護と神経新生について-

    2010年01月 - 2011年03月

    財団法人てんかん治療研究振興財団  財団法人てんかん治療研究振興財団研究助成 

    安原隆雄, 伊達 勲, 上利 崇

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1600000円 ( 直接経費:1600000円 )

    これまで我々は、キンドリングやカイニン酸を用いたてんかんモデルラットに対して、エリスロポイエチン持続脳室内投与や細胞移植、電気刺激などの手法を用いて、その治療効果や神経新生に与える影響を評価してきた。いずれの治療法も有効であり、さらに、異常な神経新生を抑制することから、てんかんに対する治療効果が得られているのではないかと考えている。これまで行ってきた治療法では、いずれも神経栄養因子であるBDNF(脳由来神経栄養因子)とその受容体であるTrkBの発現が影響を受けていることも明らかであり、今回の研究では、直接BDNFを産生する細胞株の移植という手法を用いて、てんかんモデルラットに対する治療効果と神経新生に与える影響を評価したいと考えている。さらに、TrkBに対する拮抗抗体を用いることにより、治療効果などがどのような影響を受けるかの評価も行う。この研究は、これまでの我々の一連の研究をつなぐ可能性があり、非常に意義深いものになると考えている。

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  • 頭部外傷モデル動物に対するカルバミル化エリスロポイエチン-ヒトIgG Fc部融合タンパク (cEPO-Fc)を用いた前臨床研究

    2010年01月 - 2011年03月

    財団法人かなえ医薬振興財団  財団法人かなえ医薬振興財団研究助成 

    安原隆雄, 菱川朋人

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1000000円 ( 直接経費:1000000円 )

    エリスロポイエチン (EPO) は造血ホルモンとして知られるだけでなく、神経保護作用があることが明らかになり、脳梗塞患者に対する臨床応用も欧米で進んでいる。一方、短い半減期や本来の作用である造血能による多血症の副作用のため、臨床応用に際しては低用量持続投与が必要である。今回、数年来の知人であるオーストリアにあるUniv. of Natural Resources and Applied Life Sciences、Katinger教授より半減期が長く、かつ造血作用が無いcEPO-Fcが供与された。(別紙参照)本研究では、真に臨床応用を目指し、cEPO-Fcの頭部外傷に対する治療効果を検討する。

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  • びまん性軸索損傷に対するリハビリと神経新生

    2009年09月 - 2010年09月

    日本損害保険協会  2009年度交通事故医療に関する一般研究助成 

    安原隆雄, 伊達 勲, 菱川朋人

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:1000000円 ( 直接経費:1000000円 )

    頭部外傷は若年者の死因の上位にある不慮の事故死の半数を占め、死を免れても重篤な後遺症を残すものが多い。交通事故による頭部外傷は高エネルギー損傷であり、しばしばびまん性軸索損傷を伴う。びまん性軸索損傷は重症頭部外傷の約半数を占め、病態概念は、頭蓋内占拠性病変によらない、外傷後6時間以上続く昏睡状態を指す。外科的治療の適応が無いことも多く、急性期を内科的加療でしのぎ、リハビリで機能回復を図らざるを得ないことも多い。実際、臨床でびまん性軸索損傷に対するリハビリ治療の意義は非常に大きく、症例によってはリハビリを続けることで機能回復が著明に得られることもある。一方、リハビリを続けても治療効果が乏しいこともある。近年の研究でリハビリによって神経新生が賦活化されることが明らかにされているが、治療効果との関係はまだ明らかではない。
    本研究で我々が明らかにしたいことは、びまん性軸索損傷モデルラットを用いて、リハビリを超急性期から開始し、その治療効果と神経新生の程度に関係があるかどうか、ということである。リハビリも複数種類行い、どのようなリハビリが有効なのか検討する。さらにリハビリが治療効果や神経新生と相関性を有する場合には、移植治療と組み合わせてリハビリを行うことにより、相乗効果が得られるかどうかということも明らかにしたい。

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  • もやもや病に対するVEGF遺伝子導入と骨髄幹細胞移植のダブル治療

    研究課題/領域番号:21591840  2009年 - 2011年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    徳永 浩司, 菱川 朋人, 亀田 雅博, 安原 隆雄, 伊達 勲, 杉生 憲志, 黒住 和彦, 上利 崇

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    資金種別:競争的資金

    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    もやもや病モデルラットに対して、血行再建術と骨髄幹細胞移植が行動学的改善をもたらすことを確認した。しかし、血行再建術に加えてVEGF遺伝子を導入しても、新生血管の有意な増加を認めるのみで、その有無による有意な行動学的改善は認められなかった。そのため血管新生因子導入と骨髄幹細胞移植のダブル治療に関しては、VEGFを超える可能性をもつ血管新生因子を探索した。その過程でapelin-APJシステムが慢性脳虚血によって惹起されることを確認した。加えて、サルを用いた血管内手技による低侵襲な脳虚血モデルの開発を行った。

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  • パーキンソン病はDBSで治るのか? : バイオマーカーによる治療効果予測と共に

    研究課題/領域番号:21591871  2009年 - 2011年

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    三好 康之, 上利 崇, 菱川 朋人, 亀田 雅博, 安原 隆雄, 伊達 勲, 市川 智継, 黒住 和彦

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    我々は、パーキンソン病の動物モデルにおける8-OHdGの経時的変化について研究を続け、早期に8-OHdGが高値を示すケースは最終的に高度のドパミン神経変性を合併することを確認し、尿中8-OHdGレベルがパーキンソン病の重症度を示す良い指標となるという結論を得た。また、臨床研究にて、パーキンソン病患者における酸化ストレスとDBSの関係について検証を行ったところ、DBSの前後で8-OHdGの値は有意に減少しており、DBSがパーキンソン病患者の酸化ストレスの軽減に寄与していることが確認できた。

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  • びまん性軸索損傷に対するヒト神経幹細胞動注療法

    2008年05月 - 2010年04月

    山陽放送学術文化財団  平成20年度研究助成 

    安原隆雄

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    担当区分:研究代表者  資金種別:競争的資金

    配分額:500000円 ( 直接経費:500000円 )

    頭部外傷は若年者の死因の上位にある不慮の事故死の半数を占め、死を免れても重篤な後遺症を残すものが多い。びまん性軸索損傷は重症頭部外傷の約半数を占め、病態概念は、頭蓋内占拠性病変によらない、外傷後6時間以上続く昏睡状態を指す。頭蓋内占拠性病変を伴わない場合は、基本的に保存的治療を行うしかないが、予後は不良であり、死亡率は30%に達するという報告もある。重症頭部外傷のガイドラインにも、びまん性軸索損傷に確固たる推奨される治療法は記載されていない。実際臨床で重症びまん性軸索損傷に遭遇した場合、低体温・バルビツレート療法により脳圧をコントロールしても、復温時の種々の合併症を乗り越えられず、著明な予後の改善は望めない。
    我々はこれまで、カプセル化細胞脳内移植をはじめ、細胞療法に対する基礎研究を行い、パーキンソン病に対して副腎髄質細胞と末梢神経を同時移植するなど、臨床応用への道を歩んできた。最近では自己幹細胞移植や神経栄養因子分泌幹細胞を用いた基礎研究を行い、幹細胞を臨床応用するのに、良いターゲットは何か検討を重ねてきた。びまん性軸索損傷では文字通り軸索が損傷されるだけでなく、微小血管をはじめとする脳内の種々の構造物が一度に損傷されるため、幹細胞のような多能性を有する細胞療法は非常に有用な治療法に成りうると考えられる。また、移植経路を考えると、脳実質内移植では出血を含めた合併症が、静脈内投与では低い細胞生着率が問題となるが、動脈内投与は侵襲と生着率において二者の中間にあることがこれまでの我々の動物研究で明らかとなっている。特に頭部外傷によって損傷を受けた脳では、血液脳関門が壊れており、細胞の遊走という点では有利な環境であると考えられる。我々の施設では多くの血管内治療を行っており、他疾患に対する基礎研究においても動脈内細胞投与は安全かつ確実に施行可能である。これらの状況から、特にびまん性軸索損傷モデルに対する神経幹細胞動脈内移植の研究を思い至った。具体的には、げっ歯類において、Fluid percussion装置によるびまん性軸索損傷モデルを作成し、1.神経幹細胞を動脈内投与すると、損傷部位に移植細胞は定着生存し、神経保護効果を示すか。2.動脈内幹細胞投与によりグリア細胞の増殖、脳浮腫、脳内のサイトカイン濃度に変化は生じるか。3.動脈内幹細胞投与は受傷後、どのタイミングが最も有用でかつ安全か。4.低体温療法やバルビツレート療法と組み合わせることによる相加・相乗効果は認められるか。といった点を明らかにする。

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  • 廃用症候群に対する骨髄幹細胞移植とリハビリを用いたダブル治療

    研究課題/領域番号:20791011  2008年 - 2009年

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    安原 隆雄

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    移植骨髄幹細胞は、健常ラット、後肢懸垂による廃用症候群モデルラット、頭部外傷モデルラットいずれにおいても、リハビリにより生存率が有意に増加した。また廃用症候群モデルラット、頭部外傷モデルラット、パーキンソン病モデルラットにおいては、リハビリによる有意な行動学的改善も得られた。廃用症候群モデルラットとパーキンソン病モデルラットにおいてはさらに、移植された骨髄幹細胞が広範に遊走していて、有意に神経前駆細胞のマーカーであるDoublecortin陽性細胞数が増加していた。リハビリは脳における神経栄養因子の発現を増強していた。

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