研究者詳細 - 佐々木　達也

論文 - 佐々木　達也

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Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke. 国際誌

Takayuki Nagase, Takao Yasuhara, Kyohei Kin, Susumu Sasada, Satoshi Kawauchi, Satoru Yabuno, Chiaki Sugahara, Yuichi Hirata, Hayato Miyake, Tatsuya Sasaki, Koji Kawai, Shun Tanimoto, Tomoya Saijo, Shota Tanaka

Experimental neurology 115145 - 115145 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ischemic stroke results in significant long-term disability and mortality worldwide. Although existing therapies, such as recombinant tissue plasminogen activator and mechanical thrombectomy, have shown promise, their application is limited by stringent conditions. Mesenchymal stem cell (MSC) transplantation, especially using SB623 cells (modified human bone marrow-derived MSCs), has emerged as a promising alternative, promoting neurogenesis and recovery. This study evaluated the effects of voluntary and forced exercise, alone and in combination with SB623 cell transplantation, on neurological and psychological outcomes in a rat model of ischemic stroke. Male Wistar rats that had undergone middle cerebral artery occlusion (MCAO) were divided into six groups: control, voluntary exercise (V-Ex), forced exercise (F-Ex), SB623 transplantation, SB623 + V-Ex, and SB623 + F-Ex. Voluntary exercise was facilitated using running wheels, while forced exercise was conducted on treadmills. Neurological recovery was assessed using the modified neurological severity score (mNSS). Psychological symptoms were evaluated through the open field test (OFT) and forced swim test (FST), and neurogenesis was assessed via BrdU labeling. Both exercise groups exhibited significant changes in body weight post-MCAO. Both exercises enhanced the treatment effect of SB623 transplantation. The forced exercise showed a stronger treatment effect on ischemic stroke than voluntary exercise alone, and the sole voluntary exercise improved depression-like behavior. The SB623 + F-Ex group demonstrated the greatest improvements in motor function, infarct area reduction, and neurogenesis. The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients.

DOI： 10.1016/j.expneurol.2025.115145

Repeated non-hemorrhagic and non-contusional mild traumatic brain injury in rats elicits behavioral impairment with microglial activation, astrogliosis, and tauopathy: Reproducible and quantitative model of chronic traumatic encephalopathy

Chiaki Sugahara, Kyohei Kin, Tatsuya Sasaki, Susumu Sasada, Satoshi Kawauchi, Satoru Yabuno, Takayuki Nagase, Takahiro Hirayama, Kaori Masai, Kakeru Hosomoto, Yosuke Okazaki, Koji Kawai, Shun Tanimoto, Yuichi Hirata, Hayato Miyake, Hiromichi Naito, Takao Yasuhara, Cesar V Borlongan, Isao Date, Shota Tanaka

Brain Research 149412 - 149412 2024年12月

A retrospective study on post-operative recovery of daily living activity after total corpus callosotomy. 国際誌

Hiroki Tsuchiya, Takashi Shibata, Tatsuya Sasaki, Mari Akiyama, Tomoyuki Akiyama, Katsuhiro Kobayashi

Brain & development 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Post-operative complications of corpus callosotomy (CC) in children, prolonged hospitalization due to inactivity as acute disconnection syndrome is occasionally experienced. We aimed to clarify this issue and its risk factors with a hypothesis that electroencephalogram (EEG) findings as measures of functional lateralization may be among prognostic factors for post-operative recovery. MATERIALS AND METHODS: Twenty-three patients with childhood-onset drug-resistant epilepsy who underwent total CC between April 2017 and December 2023 were included in the study and they were divided into two groups based on the duration of post-operative hospitalization as an indicator of recovery of daily living activity. We compared scalp EEG findings and the other factors including clinical characteristics between the two groups. RESULTS: Of 22 patients (14 males) without specific complications, post-operative hospitalization clustered in 9-14 days in 15 patients (Group A) with range 16-118 days in seven patients (Group B). The ratios of patients with non-lateralized spikes on pre-operative EEG and that of patients with symmetric background activity on post-operative EEG were significantly greater in Group B (7/7, 100 %; 6/7, 86 %, respectively) than in Group A (8/15, 53 %; 4/15, 27 %, respectively) (p = 0.038; p = 0.020, respectively, by Fisher's exact test), while other factors were not significantly different between the two groups. CONCLUSIONS: Delayed recovery of living activity should be anticipated, especially in patients with non-lateralized epileptic discharges on pre-operative EEG.

DOI： 10.1016/j.braindev.2024.09.006

Cervical spinal cord stimulation exerts anti-epileptic effects in a rat model of epileptic seizure through the suppression of CCL2-mediated cascades. 国際誌

Yosuke Okazaki, Tatsuya Sasaki, Kakeru Hosomoto, Shun Tanimoto, Koji Kawai, Takayuki Nagase, Chiaki Sugahara, Satoru Yabuno, Kyohei Kin, Susumu Sasada, Takao Yasuhara, Shota Tanaka, Isao Date

Scientific reports 14 ( 1 ) 14543 - 14543 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure.

DOI： 10.1038/s41598-024-64972-y

広範な脳形成異常に伴う新生児期発症難治てんかんに対して緩和的半球離断術を施行した1乳児例

兵頭勇紀, 松田奈央子, 金聖泰, 秋山麻里, 佐々木達也, 秋山倫之, 小林勝弘

てんかん研究 42 ( 1 ) 58 - 58 2024年6月

8歳MRI陰性側頭葉てんかんの一手術例

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

てんかん研究 42 ( 1 ) 58 - 59 2024年6月

新生児低血糖症による両側後頭葉病変を背景としたWest症候群の1手術例

竹中暁, 土屋弘樹, 柴田敬, 所谷知穂, 佐々木達也, 伊達勲, 秋山倫之, 小林勝弘

てんかん研究 42 ( 1 ) 64 - 64 2024年6月

脳腫瘍摘出術後に発作の完全抑制を得られた乳児てんかん性スパズム症候群の男児例

塚原理恵, 土屋弘樹, 秋山麻里, 佐々木達也, 秋山倫之, 小林勝弘

てんかん研究 42 ( 1 ) 77 - 77 2024年6月

脳活動の発振大脳基底核の脳機能制御パーキンソン病に対する迷走神経刺激療法の意義当科での基礎研究から得られた知見

谷本駿, 佐々木達也, 金一徹, 細本翔, 岡崎洋介, 皮居巧嗣, 佐々田晋, 金恭平, 藪野諭, 菅原千明, 永瀬喬之, 平田雄一, 三宅隼人, 安原隆雄, 伊達勲

日本定位・機能神経外科学会プログラム・抄録集 63回 76 - 76 2024年1月

Parkinson病の姿勢異常と電気刺激療法招待

安原隆雄、佐々田晋、馬越通有、三好康之、佐々木達也、伊達勲

脊椎脊髄ジャーナル 36 ( 9 ) 661 - 666 2023年10月

Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma.

Hiroki Tsuchiya, Takashi Shibata, Tatsuya Sasaki, Takushi Inoue, Isao Date, Tomoyuki Akiyama, Katsuhiro Kobayashi

Acta medica Okayama 77 ( 5 ) 561 - 566 2023年10月

記述言語：英語

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity.

DOI： 10.18926/AMO/65980

Correction: Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke. 国際誌

Satoru Yabuno, Takao Yasuhara, Takayuki Nagase, Satoshi Kawauchi, Chiaki Sugahara, Yosuke Okazaki, Kakeru Hosomoto, Susumu Sasada, Tatsuya Sasaki, Naoki Tajiri, Cesar V Borlongan, Isao Date

Stem cell research & therapy 14 ( 1 ) 123 - 123 2023年5月

脳梁離断術後の活動性低下,食思不振が長期化しうる要因とは

土屋弘樹, 大野友香子, 道上理絵, 柴田敬, 秋山麻里, 佐々木達也, 伊達勲, 秋山倫之, 小林勝弘

脳と発達 55 ( Suppl. ) S281 - S281 2023年5月

一次運動野付近にてんかん原性領域を疑われ,術式選択に苦慮したWest症候群の1例

時岡礼恵, 土屋弘樹, 秋山倫之, 佐々木達也, 伊達勲, 小林勝弘

脳と発達 55 ( Suppl. ) S281 - S281 2023年5月

結節性硬化症を背景とした焦点てんかんの生後2ヵ月児に対する早期てんかん外科治療の1例

竹中暁, 品川穣, 秋山麻里, 柴田敬, 土屋弘樹, 秋山倫之, 佐々木達也, 伊達勲, 小林勝弘

脳と発達 55 ( Suppl. ) S423 - S423 2023年5月

一次運動野付近にてんかん原性領域を疑われ,術式選択に苦慮したWest症候群の1例

時岡礼恵, 土屋弘樹, 秋山倫之, 佐々木達也, 伊達勲, 小林勝弘

脳と発達 55 ( Suppl. ) S281 - S281 2023年5月

結節性硬化症を背景とした焦点てんかんの生後2ヵ月児に対する早期てんかん外科治療の1例

竹中暁, 品川穣, 秋山麻里, 柴田敬, 土屋弘樹, 秋山倫之, 佐々木達也, 伊達勲, 小林勝弘

脳と発達 55 ( Suppl. ) S423 - S423 2023年5月

脳梁離断術後の活動性低下,食思不振が長期化しうる要因とは

土屋弘樹, 大野友香子, 道上理絵, 柴田敬, 秋山麻里, 佐々木達也, 伊達勲, 秋山倫之, 小林勝弘

脳と発達 55 ( Suppl. ) S281 - S281 2023年5月

がんゲノム医療がもたらす小児脳腫瘍の展開当院における小児グリオーマ診療についてがんゲノム医療時代における変遷

石田穣治, 大谷理浩, 藤井謙太郎, 佐々木達也, 鷲尾佳奈, 柳井広之, 遠西大輔, 山本英喜, 伊達勲

小児の脳神経 48 ( 2 ) 153 - 153 2023年4月

おもり自由落下装置を用いた慢性頭部外傷性脳症モデルの作成高い再現性と定量性を求めて

菅原千明, 安原隆雄, 平山隆浩, 正井加織, 佐々田晋, 河内哲, 藪野諭, 永瀬喬之, 佐々木達也, 内藤宏道, 浅沼幹人, 伊達勲

日本脳神経外傷学会プログラム・抄録集 46回 119 - 119 2023年2月

Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke. 国際誌

Satoru Yabuno, Takao Yasuhara, Takayuki Nagase, Satoshi Kawauchi, Chiaki Sugahara, Yosuke Okazaki, Kakeru Hosomoto, Susumu Sasada, Tatsuya Sasaki, Naoki Tajiri, Cesar V Borlongan, Isao Date

Stem cell research & therapy 14 ( 1 ) 10 - 10 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke. METHODS: Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 105 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups. RESULTS: SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05). CONCLUSIONS: This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF.

DOI： 10.1186/s13287-023-03236-4

Continuous vagus nerve stimulation exerts beneficial effects on rats with experimentally induced Parkinson's disease: Evidence suggesting involvement of a vagal afferent pathway. 国際誌

Kakeru Hosomoto, Tatsuya Sasaki, Takao Yasuhara, Masahiro Kameda, Susumu Sasada, Ittetsu Kin, Ken Kuwahara, Satoshi Kawauchi, Yosuke Okazaki, Satoru Yabuno, Chiaki Sugahara, Koji Kawai, Takayuki Nagase, Shun Tanimoto, Cesario V Borlongan, Isao Date

Brain stimulation 16 ( 2 ) 594 - 603 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined. OBJECTIVE: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats. METHODS: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively. RESULTS: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects. CONCLUSION: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes.

DOI： 10.1016/j.brs.2023.03.003

IDH-mutant Astrocytoma Arising in the Brainstem with Symptom Improvement by Foramen Magnum Decompression: A Case Report.

Takayuki Nagase, Joji Ishida, Susumu Sasada, Tatsuya Sasaki, Yoshihiro Otani, Satoru Yabuno, Kentaro Fujii, Atsuhito Uneda, Takao Yasuhara, Isao Date

NMC case report journal 10 75 - 80 2023年

記述言語：英語

Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.

DOI： 10.2176/jns-nmc.2022-0159

パーキンソン病患者の脊椎と姿勢を考える招待

安原隆雄、佐々田晋、馬越通有、岡崎三保子、三好康之、佐々木達也、伊達勲

脊髄外科 SPINAL SURGERY 36 ( 3 ) 248 - 256 2022年12月

機能神経外科における感染─デバイスを用いた手術を中心に─ 招待

佐々木達也、安原隆雄、伊達勲

脳神経外科 50 ( 5 ) 1027 - 1034 2022年9月

[Infections in Functional Neurosurgery:Focusing on Device-based Surgery].

Tatsuya Sasaki, Takao Yasuhara, Isao Date

No shinkei geka. Neurological surgery 50 ( 5 ) 1027 - 1034 2022年9月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Functional neurosurgery for epilepsy, movement disorders, and spasticity includes some device-based surgeries such as deep brain stimulation, subdural electrode placement, vagus nerve stimulation, and baclofen pump implantation. These surgeries have a higher risk of surgical site infection(SSI)than other general neurological surgeries. Furthermore, because device removal after infection can significantly impair patients'activities of daily living and quality of life, SSI in functional neurosurgery is a worrisome surgical complication. In this study, we conducted a mini-review of the risk of infection in each device-based surgery and described associated surgical procedures and preparations performed at our institution, with a focus on infection prevention.

DOI： 10.11477/mf.1436204662

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats 査読国際誌

Kawauchi S, Yasuahra T, Kin K, Yabuno S, Sugahara C, Nagase T, Hosomoto K, Okazaki Y, Tomita Y, Umakoshi M, Sasaki T, Kameda M, Borlongan CV, Date I

CNS Neuroscience & Therapeutics 28 ( 12 ) 1974 - 1985 2022年8月

当院における小児のてんかん外科の手術 focal epilepsyとepileptic spasmの治療方針の決定について

佐々木達也, 細本翔, 岡崎洋介, 谷本駿, 皮居巧嗣, 佐々田晋, 安原隆雄, 土屋弘樹, 秋山倫之, 小林勝弘, 伊達勲

てんかん研究 40 ( 2 ) 401 - 401 2022年8月

当院における小児のてんかん外科の手術 focal epilepsyとepileptic spasmの治療方針の決定について

佐々木達也, 細本翔, 岡崎洋介, 谷本駿, 皮居巧嗣, 佐々田晋, 安原隆雄, 土屋弘樹, 秋山倫之, 小林勝弘, 伊達勲

てんかん研究 40 ( 2 ) 401 - 401 2022年8月

A Case of a Solitary Cortical Tuber with No Other Manifestations of Tuberous Sclerosis Complex Mimicking Focal Cortical Dysplasia Type II with Calcification.

Kakeru Hosomoto, Tatsuya Sasaki, Koji Kawai, Yosuke Okazaki, Yuki Hyodo, Takashi Shibata, Susumu Sasada, Takao Yasuhara, Katsuhiro Kobayashi, Hiroyuki Yanai, Isao Date

Acta medica Okayama 76 ( 3 ) 323 - 328 2022年6月

記述言語：英語

Cortical tubers are one of the typical intracranial manifestations of tuberous sclerosis complex (TSC). Multiple cortical tubers are easy to diagnose as TSC; however, a solitary cortical tuber without any other cutaneous or visceral organ manifestations can be confused with other conditions, particularly focal cortical dysplasia. We report a surgical case of refractory epilepsy caused by a solitary cortical tuber mimicking focal cortical dysplasia type II, and describe the radiological, electrophysiological, and histopathological findings of our case.

DOI： 10.18926/AMO/63742

標準的な内科治療でなかなか改善しない本態性振戦─外科治療による振戦の治療─ 招待

佐々木達也、伊達勲

BRAIN and NERVE 74 ( 5 ) 645 - 651 2022年5月

[Essential Tremor That is Difficult to Improve with Standard Medical Treatment-Suppression: Surgical Treatment of Tremor].

Tatsuya Sasaki, Isao Date

Brain and nerve = Shinkei kenkyu no shinpo 74 ( 5 ) 645 - 651 2022年5月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Drug-refractory essential tremors, especially those in the upper extremities, may benefit from surgical treatment. Currently, three main treatment methods are available: deep brain stimulation (DBS), radiofrequency coagulation (RF), and magnetic resonance -guided focused ultrasound surgery (MRgFUS). DBS is a device-based therapy, and its effects are reversible, whereas RF and FUS create irreversible coagulation lesions. DBS and RF require the direct puncturing of the target, whereas FUS focuses ultrasound from extracranial sources. The primary target is the ventralis intermedius of the thalamus (Vim); however, the posterior subthalamic area (PSA) is also reportedly an effective target site. In this article, we will summarize the features of the three treatments for essential tremors, and discuss the treatment strategies and methods for each symptom.

DOI： 10.11477/mf.1416202092

あすを創る人材育成・働き方改革定位脳手術の現在・将来の役割とスキル習得 DBS、脳生検、細胞移植、ウイルス・遺伝子療法、SEEG

佐々木達也, 細本翔, 岡崎洋介, 皮居巧嗣, 大谷理浩, 佐々田晋, 石田穣治, 藤井謙太郎, 安原隆雄, 伊達勲

日本定位・機能神経外科学会プログラム・抄録集 61回 66 - 66 2022年1月

当科におけるLeksell定位脳生検術の有用性と課題

皮居巧嗣, 佐々木達也, 岡崎洋介, 細本翔, 畝田篤仁, 大谷理浩, 石田穣治, 藤井謙太郎, 佐々田晋, 安原隆雄, 伊達勲

日本定位・機能神経外科学会プログラム・抄録集 61回 139 - 139 2022年1月

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, 岡崎洋介, 皮居巧嗣, 永瀬喬之, 菅原千明, 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

日本定位・機能神経外科学会プログラム・抄録集 61回 130 - 130 2022年1月

神経症状の急激な悪化のため早急に手術し、予後良好であった非骨傷性頸椎疾患症例の検討

菅原千明, 安原隆雄, 佐々田晋, 河内哲, 藪野諭, 永瀬喬之, 佐々木達也, 伊達勲

日本脳神経外傷学会プログラム・抄録集 45回 125 - 125 2022年1月

Two Cases of Monozygotic Twins with Early-onset Isolated (DYT1) Dystonia Effectively Treated with Bilateral Globus Pallidus Internus Stimulation.

Yosuke Okazaki, Tatsuya Sasaki, Kouji Kawai, Kakeru Hosomoto, Susumu Sasada, Takao Yasuhara, Tomoyuki Akiyama, Yoshiyuki Hanaoka, Isao Date

NMC case report journal 9 307 - 312 2022年

記述言語：英語

Early-onset isolated (DYT1) dystonia is one of the most common forms of primary dystonia in childhood, and deep brain stimulation of the globus pallidus internus (GPi-DBS) is a highly effective treatment for it. However, the effectiveness of GPi-DBS in monozygotic twins with DYT1 dystonia has never been reported globally. Here, we report the cases of monozygotic twins with DYT1 dystonia who were treated using GPi-DBS, and we include a literature review. The younger brother showed an abnormal gait, with external rotation of the right lower leg at 6 years old. The symptoms gradually became so severe that he had difficulty walking on his own at 9 years of age. Treatment with levodopa-carbidopa partially resolved his symptoms, but most of the symptoms remained. Meanwhile, the older brother developed dystonia in both upper limbs at 8 years of age, with gradual symptom progression. At 13 years of age, they were diagnosed with DYT1 dystonia. Bilateral GPi-DBS was performed in both patients at 16 years of age. Their symptoms remarkably improved after surgery. The Burke-Fahn-Marsden dystonia rating scale (BFMDRS) movement score was reduced from 52 to 2 points for the younger brother and from 35 to 1 point for the older brother. Even if monozygotic twins have the same genes, the onset and severity of symptoms might vary in accordance with differences in epigenomic profiles. However, GPi-DBS treatment was very effective for the two cases; thus, we should consider the surgical interventions for each patient.

DOI： 10.2176/jns-nmc.2022-0084

Growth Curves for Intracranial Volume and Two-dimensional Parameters for Japanese Children without Cranial Abnormality: Toward Treatment of Craniosynostosis.

Yousuke Tomita, Masahiro Kameda, Takaya Senoo, Eijiro Tokuyama, Chiaki Sugahara, Satoru Yabuno, Yosuke Okazaki, Satoshi Kawauchi, Kakeru Hosomoto, Tatsuya Sasaki, Takao Yasuhara, Isao Date

Neurologia medico-chirurgica 62 ( 2 ) 89 - 96 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

In the management of patients with craniosynostosis, it is important to understand growth curve of the normal cranium. Although three-dimensional (3D) computed tomography (CT) images taken in thin slices are easily available nowadays, data on the growth curves of intracranial volume (ICV), cranial length, cranial width, and cranial height in the normal cranium are mainly based on older studies using radiography, and there are insufficient reports using CT images especially taken in thin slices. The purpose of this study was to establish growth curves in the normal cranium of Japanese children using thin-slice images. Cranial images of 106 subjects (57 males, 49 females; aged 0-83 months) without significant cranial abnormalities were retrospectively analyzed. Using thin-slice CT images, the ICV and two-dimensional parameters such as cranial length, cranial width, and cranial height were measured by iPlan, followed by generating growth curves and calculating cephalic index (CI). ICV calculated from thin-slice CT images was compared with that obtained by substituting two-dimensional parameters into Mackinnon formula. The ICV growth curves for males and females were similar in shape. As with the ICV, the two-dimensional parameters increased most rapidly in the first year after birth. There was no significant difference in CI between the sexes or among any age groups. ICV calculated from thin-slice 3D CT images was 60% of that obtained from Mackinnon formula. These data will enable us to compare these specific measurements in craniosynostosis patients directly with those of normal children, which will hopefully help in managing these patients.

DOI： 10.2176/nmc.oa.2021-0208

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

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

DBSの刺激調整法とデバイスの特徴招待

佐々木達也、伊達勲

脳神経外科 49 ( 4 ) 829 - 837 2021年7月

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

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

[Programing of Deep Brain Stimulation and Features of Devices].

Tatsuya Sasaki, Isao Date

No shinkei geka. Neurological surgery 49 ( 4 ) 829 - 837 2021年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Deep brain stimulation(DBS)is an effective therapy for conditions involving drug-resistant involuntary movements, such as Parkinson's disease, tremor, and dystonia. Programming of DBS, as well as strict surgical indications, appropriate target selection, and accurate electrode placement, is one of the most important factors in the success of DBS. To obtain effective stimulation for a long period, it is important to expand the therapeutic window and reduce side effects. Recent advances in DBS devices have dramatically expanded the variety of stimulus settings. While the indication criteria of DBS and surgical techniques have been established, the details of the programming algorithm are not yet unified. In this paper, we describe the features of each device, basic programming methods, management of DBS-related side effects, and advanced stimulus methods.

DOI： 10.11477/mf.1436204461

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

日本定位・機能神経外科学会プログラム・抄録集 60回 110 - 110 2020年12月

Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells and counteracts depressive-like behavior of treatment-resistant depressed rats. 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 2020年6月

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

Cell therapy for central nervous system disorders: Current obstacles to progress. 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

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

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

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

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

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

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.

DOI： 10.3389/fnagi.2020.00164

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

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

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.

DOI： 10.1093/ons/opy351

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

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.

DOI： 10.1016/j.brainres.2019.04.001

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

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

A new approach for implantation of a cardiac resynchronization therapy-defibrillator in a patient with bilateral pectoral neurostimulation devices. 国際誌

Saori Tsukuda, Nobuhiro Nishii, Yoshiaki Inoue, Tatsuya Sasaki, Hiroshi Morita, Hiroshi Ito

HeartRhythm case reports 4 ( 10 ) 444 - 446 2018年10月

[Devices and Practices for Improving the Accuracy of Deep Brain Stimulation].

Tatsuya Sasaki, Takashi Agari, Isao Date

No shinkei geka. Neurological surgery 46 ( 9 ) 751 - 762 2018年9月

乳児脳室外上衣下巨細胞性星細胞腫の一例

坪井伸成, 黒住和彦, 佐々木達也, 柳井広之, 伊達勲

Brain Tumor Pathology 35 ( Suppl. ) 166 - 166 2018年9月

Hemodynamic features of offending vessels at neurovascular contact in patients with trigeminal neuralgia and hemifacial spasm. 国際誌

Toru Satoh, Takanobu Yagi, Keisuke Onoda, Masahiro Kameda, Tatsuya Sasaki, Tomotsugu Ichikawa, Isao Date

Journal of neurosurgery 1 - 7 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVEOffending vessels at the site of neurovascular contact (NVC) in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS) may have specific hemodynamic features. The purpose of this study was to investigate the wall shear stress (WSS) of offending vessels at NVCs by conducting a computational fluid dynamics (CFD) analysis.METHODSThe authors retrospectively analyzed the cases of 20 patients (10 with TN and 10 with HFS) evaluated by 3D CT angiography and used the imaging findings for analysis of the hemodynamic parameters. The 3D CFD images were directly compared with the NVCs determined by simulated multifusion images of CT angiogram and MR cisternogram, and operative photos. The magnitudes of the WSS (WSSm) at the proximal (WSSm-p), just-beginning (WSSm-j), contact site (WSSm-s), and distal (WSSm-d) areas of each NVC were analyzed. The ratios of the WSSm-j, WSSm-s, and WSSm-d areas to the WSSm-p area were calculated individually. The direction of the WSS (WSSv) and its temporal variation (WSSvV) were depicted and morphologically compared with the NVC confirmed by simulated images and operative findings.RESULTSThe ratios of WSSm at the just-beginning and the contact site to the proximal area of the NVCs (WSSm-j/WSSm-p and WSSm-s/WSSm-p) were both significantly higher than that at the distal area (WSSm-d/WSSm-p) (p < 0.05). The WSSv and WSSvV at the NVCs showed small variation in a single cardiac cycle, especially along the areas that were in contact with the affected nerve.CONCLUSIONSAreas of relatively high WSSm and temporal variation of WSSm (WSSmV) were observed at the NVCs. Less mobility of the WSSv and WSSvV was detected along the side of the vessels in contact with the nerves. These findings may be consistent with the actual area of the NVC. Hemodynamic features of the site of NVC can be added to the preoperative simulation for MVD surgery, which may be useful for the diagnosis and treatment planning of TN and HFS.

DOI： 10.3171/2018.1.JNS172544

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

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

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

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

多様な画像所見を呈したmultifocal dysembryoplastic neuroepithelial tumorの1例

佐々木達也, 亀田雅博, 冨田陽介, 細本翔, 林裕美子, 遠藤文香, 岡牧郎, 冨田祐介, 安原隆雄, 上利崇, 小林勝弘, 伊達勲

脳神経外科ジャーナル 27 ( 4 ) 317 - 323 2018年4月

記述言語：日本語出版者・発行元：(一社)日本脳神経外科コングレス

症例は側頭葉てんかんを発症した13歳男児。頭部MRIで右側頭葉内広範囲、基底核、深部白質、側脳室内などに多発する病変を認め、さらに経時的に造影病変は変化した。Fluorodeoxyglucose-positron emission tomography(FDG-PET)で悪性を示唆する所見はなく、subtraction ictal single-photon emission computed tomography coregistered to MRI(SISCOM)と発作時脳波で右側頭葉が発作焦点であると判断し、一期的に右側頭葉切除を行った。病理学的診断はdysembryoplastic neuroepithelial tumorであった。現時点で術後半年経過したが、発作は消失し、残存病変についても増大していない。多発性DNTは非常にまれであり、変化に富む画像所見とあわせて、治療方針の決定に難渋した。本症例はてんかんの治療目的に手術を行ったが、複雑な病態であっても、治療目的を明確にし、それに応じた検査、手術を行うことが重要である。(著者抄録)

その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02632&link_issn=&doc_id=20180403310006&doc_link_id=10.7887%2Fjcns.27.317&url=https%3A%2F%2Fdoi.org%2F10.7887%2Fjcns.27.317&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

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

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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

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

Multifocal dysembryoplastic neuroepithelial tumor showing various imaging findings: A case report 査読

Tatsuya Sasaki, Masahiro Kameda, Yosuke Tomita, Kakeru Hosomoto, Yumiko Hayashi, Fumika Endoh, Makio Oka, Yusuke Tomita, Takao Yasuhara, Takashi Agari, Katsuhiro Kobayashi, Isao Date

Japanese Journal of Neurosurgery 27 ( 4 ) 317 - 322 2018年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Japanese Congress of Neurological Surgeons

Dysembryoplastic neuroepithelial tumor (DNT) is a type of brain tumor that causes refractory epilepsy. We present the case of a 13-year-old boy with temporal lobe epilepsy. Magnetic resonance imaging (MRI) revealed multiple lesions in the right temporal lobe, basal ganglia, deep white matter, and lateral ventricle. Serial MRI showed morphological changes of contrast-enhanced lesions, but fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed hypometabolic lesions. Subtraction ictal single-photon emission computed tomography coregistered to MRI (SISCOM) and ictal electroencephalography (EEG) suggested the seizure onset zone might be located in the right temporal lobe. We performed right temporal lobectomy, and pathological diagnosis confirmed DNT. At one year post-surgery, the patient has achieved seizure-free status, and the remaining lesions have not increased. Multifocal DNT is extremely rare, and treatment strategy was difficult to determine in this case. Surgery should be performed when appropriate after clarifying the treatment purpose.

DOI： 10.7887/jcns.27.317

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

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

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

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

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

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

Significance of High-frequency Electrical Brain Activity.

Katsuhiro Kobayashi, Tomoyuki Akiyama, Takashi Agari, Tatsuya Sasaki, Takashi Shibata, Yoshiyuki Hanaoka, Mari Akiyama, Fumika Endoh, Makio Oka, Isao Date

Acta medica Okayama 71 ( 3 ) 191 - 200 2017年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (< 0.1 Hz) to traditional frequency bands (e.g., the approx. 10 Hz alpha rhythm) to high-frequency bands of up to 500 Hz. High-frequency oscillations (HFOs) including ripple and fast ripple oscillations (80-200 Hz and>200 / 250 Hz, respectively) are particularly of note due to their very close relationship to epileptogenicity, with the possibility that they could function as a surrogate biomarker of epileptogenicity. In contrast, physiological high-frequency activity plays an important role in higher brain functions, and the differentiation between pathological / epileptic and physiological HFOs is a critical issue, especially in epilepsy surgery. HFOs were initially recorded with intracranial electrodes in patients with intractable epilepsy as part of a long-term invasive seizure monitoring study. However, fast oscillations (FOs) in the ripple and gamma bands (40-80 Hz) are now noninvasively detected by scalp EEG and magnetoencephalography, and thus the scope of studies on HFOs /FOs is rapidly expanding.

DOI： 10.18926/AMO/55201

[Surgical Technique and Memory Outcome of Transsylvian Hippocampal Transection in 24 Patients with MRI-Negative Temporal Lobe Epilepsy].

Michiharu Morino, Sachiko Takamizawa, Chika Yoshimura, Tatsuya Sasaki

No shinkei geka. Neurological surgery 45 ( 3 ) 199 - 209 2017年3月

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

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

[Stent-Assisted Coil Embolization of a Dissecting Aneurysm of the Posterior Cerebral Artery: A Case Report].

Jun Haruma, Kenji Sugiu, Tadato Yukiue, Tatsuya Sasaki, Yasuhiko Hattori, Kazuki Kobayashi, Hideyuki Yoshida, Koji Muneda, Isao Date

No shinkei geka. Neurological surgery 43 ( 12 ) 1099 - 104 2015年12月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Dissecting aneurysms of the posterior cerebral artery (PCA) are rare, especially those at the P1 segment. Here, we describe the case of a 57-year-old woman with a subarachnoid hemorrhage (SAH). Computed tomography angiography (CTA) and digital subtraction angiography (DSA) revealed a small (3 mm) dissecting aneurysm with the typical pearl-and-string sign at the right P1 segment. Fourteen days after onset, the patient developed aphasia. DSA revealed vasospasm of the right middle cerebral artery, and we performed endovascular treatment by the intra-arterial injection of 1-(5-isoquinolinesulfonyl) homopiperazine. After this treatment, the patient's symptoms recovered immediately. Vertebral angiography revealed enlargement of the dissecting aneurysm (up to 7 mm diameter). We started a loading dose of 300 mg aspirin and 400 mg clopidogrel after observing growth of the aneurysm. Fifteen days after onset, we performed a stent-assisted coil embolization, and obtained nearly complete obliteration of the aneurysm with preserved patency of the parent artery. Six-month follow-up DSA demonstrated complete occlusion of the aneurysm with good patency of the stented PCA; the patient was at modified Rankin Scale 1. In the treatment of ruptured dissecting aneurysms, parent vessel occlusion (PVO) with aneurysm is common. However, PVO may cause both cerebral infarction of the distal area and perforator occlusion of the occluded vessel. Stent-assisted coil embolization can preserve parent vessel flow and obliterate the aneurysm. Stents offer a therapeutic alternative for PCA dissecting aneurysms, especially when PVO cannot be tolerated.

DOI： 10.11477/mf.1436203187

[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

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

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

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.

DOI： 10.1371/journal.pone.0127302

Cognitive functions in Parkinson's disease: Relation to disease severity and hallucination

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

Parkinsonism and Related Disorders 20 ( 4 ) 415 - 420 2014年4月

記述言語：英語

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.

DOI： 10.1016/j.parkreldis.2014.01.002

Neuroprotective Effects of Liraglutide for Stroke Model of Rats 査読

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 - 21524 2013年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

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

[Pyoktanin blue injection for resection of cystic brain tumor: a case report]. 査読

Yusuke Tomita, Tatsuya Sasaki, Tomoyuki Tanabe, Masaru Idei, Kenichiro Muraoka, Kinya Terada, Toshinari Meguro, Nobuyuki Hirotsune, Shigeki Nishino

No shinkei geka. Neurological surgery 41 ( 8 ) 687 - 91 2013年8月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Pyoktanin blue is an agent that is often used during STA-MCA anastomosis. In this report, we inject it into a cystic tumor for complete resection, and we report its usefulness. The patient was a 57-year-old female. She suffered from progressive cerebellar ataxia. CT and MR showed a cystic metastatic tumor at the right cerebellar hemisphere, 40mm in diameter. Craniotomy was performed, 5cm in diameter, using the right suboccipital approach. After peeling off the tumor from the surface layer of the brain, we injected diluted pyoktanin blue into the tumor to dye the inside wall. After that, the tumor was peeled off completely without exposing the dyed inside wall. We sometimes find it difficult to distinguish tumor from brain if there is tearing of the tumor wall. Tearing of the tumor can be prevented by injecting pyoktanin blue into it, and making the inside wall visible. Using this procedure, we think a tumor can be resected without residual tumor or damage to the brain. Although we have used this method only a few times, we think it is an easy and useful technique to inject pyoktanin blue into a cystic tumor during its resection.

後方1/4離断術が奏功した大田原症候群の一例

上利崇, 近藤聡彦, 秋山倫之, 林裕美子, 桃木恵美子, 井上拓志, 岡牧郎, 小林勝弘, 佐々木達也, 金恭平, 伊達勲

てんかん研究 31 ( 1 ) 90 - 91 2013年6月

側頭葉てんかんにおける海馬機能の評価に対する選択的後大脳動脈ワダテストの有用性

上利崇, 井上拓志, 岡牧郎, 佐々木達也, 大谷理浩, 大塚頌子, 伊達勲

てんかん研究 30 ( 1 ) 75 - 76 2012年6月

[A case of cavernous sinus dural arteriovenous fistula presenting with intracranial hemorrhage].

Toshinari Meguro, Tatsuya Sasaki, Jun Haruma, Tomoyuki Tanabe, Kenichiro Muraoka, Kinya Terada, Nobuyuki Hirotsune, Shigeki Nishino

No shinkei geka. Neurological surgery 39 ( 7 ) 687 - 92 2011年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Intracranial cavernous sinus dural arteriovenous fistula (CS-dAVF) rarely causes intracranial hemorrhage. We report a case of CS-dAVF presenting with intracranial hemorrhage. A 62-year-old man presented tonic clonic convulsion with consciousness disturbance and was transferred to our hospital. CT scan revealed subarachnoid hemorrhage and right frontal subcortical hemorrhage. Angiography revealed right CS-dAVF which drained only into the vein of the right sylvian fissure. Transvenous embolization was performed using detachable coils. After embolization, CS-dAVF had completely disappeared and the patient was discharged without any symptom. We summarized the fourteen reported cases, including ours, of CS-dAVF with intracranial hemorrhage. All of them had retrograde drainage through cerebral veins.

Unusual cisternal coil migration in the follow-up period after aneurysm perforation during endovascular coiling.

Toshinari Meguro, Tatsuya Sasaki, Jun Haruma, Tomoyuki Tanabe, Kenichiro Muraoka, Kinya Terada, Nobuyuki Hirotsune, Shigeki Nishino

Neurologia medico-chirurgica 51 ( 5 ) 365 - 7 2011年

記述言語：英語掲載種別：研究論文（学術雑誌）

A 61-year-old woman suffered cisternal coil migration in the follow-up period after endovascular coil embolization for a ruptured cerebral aneurysm. She presented with sudden onset of headache. Computed tomography demonstrated diffuse subarachnoid hemorrhage, and cerebral angiography disclosed a left anterior choroidal artery aneurysm. The aneurysm was treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure, the microcatheter perforated the aneurysm. For direct closure of the perforation site with coils, the microcatheter was withdrawn and coils were deployed partially in the subarachnoid space and partially in the aneurysm sac. The coil mass was spread in the subarachnoid space around the aneurysm immediately after embolization. The patient was discharged with no neurological deficit. Three months later, follow-up radiography demonstrated obvious reduction in the size and compaction of the coil mass. Magnetic resonance angiography and digital subtraction angiography demonstrated stable occlusion of the aneurysm. The coil mass probably spread in the cistern around the aneurysm and was compacted by the shape memory of the coils and pulsation of the brain and vessels, as the subarachnoid clots around the aneurysm had disappeared. This case suggests that cisternal coil migration should be considered in the follow up of intracranial aneurysm treated with detachable coils.

[Transient homonymous hemianopsia due to thrombosis of the confluence of sinuses after occipital transtentorial removal of pineal region tumor].

Toshinari Meguro, Tatsuya Sasaki, Jun Haruma, Tomoyuki Tanabe, Kenichiro Muraoka, Kinya Terada, Nobuyuki Hirotsune, Shigeki Nishino

No shinkei geka. Neurological surgery 38 ( 10 ) 927 - 31 2010年10月

記述言語：日本語掲載種別：研究論文（学術雑誌）

The authors report a case of 74-year-old woman suffering thrombosis of the confluence of sinuses after the left occipital transtentorial removal of a pineal region epidermoid cyst. Four days after the operation, the patient developed left homonymous hemianopsia. Magnetic resonance imaging revealed a venous infarct in the right occipital lobe and magnetic resonance venography disclosed a signal defect of the posterior part of the confluence of sinuses. The patients' neurological symptom recovered soon after anticoagulation treatment, and magnetic resonance venography after the sixth week showed recanalization of the confluence of sinuses. Although it might be rare, thrombosis of the dural sinus should be recognized as a complication of craniotomy.

[Arterial stenosis after coil migration in embolization of an aneurysm].

Toshinari Meguro, Tatsuya Sasaki, Jun Haruma, Tomoyuki Tanabe, Kenichiro Muraoka, Kinya Terada, Nobuyuki Hirotsune, Shigeki Nishino

No shinkei geka. Neurological surgery 38 ( 1 ) 41 - 5 2010年1月

記述言語：日本語掲載種別：研究論文（学術雑誌）

A case of arterial stenosis after coil migration in intracranial aneurysm embolization is presented. A 51-year-old woman suffered sudden onset of headache and unconsciousness. Computed tomography demonstrated diffuse subarachnoid hemorrhage and cerebral angiography disclosed a right internal carotid artery (ICA) bifurcation aneurysm and a right ICA-anterior choroidal artery aneurysm. The aneurysms were treated by endovascular embolization with Guglielmi detachable coils. During the embolization procedure of the ICA bifurcation aneurysm, a coil strand detached in the sac had migrated into the ICA. We did not retrieve the migrated coil, because the free coil strand was stable in the ICA and did not cause distal flow reduction. The patient suffered vasospasm of the right ICA and underwent intra-arterial infusion of fasudil hydrochloride and percutaneous transluminal angioplasty of the ICA on day 9. The patient experienced infarction in the territory of the right anterior cerebral artery area and needed a ventriculo-peritoneal shunt for hydrocephalus. The patient was discharged with mild right hemiparesis. Follow-up angiography after six months revealed right ICA and middle cerebral artery stenosis, but the free strand of the migrated coil had not moved in the right ICA. We suspect that the coil strand might have induced thrombosis or intimal hyperplasia of the proximal M1 segment and right ICA. Although late stenosis of the parent artery might be rare, it should be recognized as a long term complication of a migrated free coil strand in the endovascular treatment of intracranial aneurysms.

[Catheter-assisted technique for endovascular treatment of a wide-neck aneurysm: a case report].

Jun Haruma, Yu Ohkuma, Tatsuya Sasaki, Tomoyuki Tanabe, Kenichiro Muraoka, Kinya Terada, Toshinari Meguro, Nobuyuki Hirotsune, Shigeki Nishino

No shinkei geka. Neurological surgery 37 ( 11 ) 1095 - 8 2009年11月

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