研究者詳細 - 金　恭平

論文 - 金　恭平

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Disc bulging predicts poor outcomes of decompression surgery for lumbar spinal canal stenosis

Kyohei Kin, Akira Kusumegi, Masashi Chinen, Shohei Okamoto, Toshiharu Mitsuhashi, Yuichi Takahashi, Kenki Nishida

European Spine Journal 2025年6月

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

Letter to the Editor. Evidence for ultra-early outcome of full endoscopic spine surgery. 国際誌

Kyohei Kin, Ryoji Tominaga, Hiroki Iwai, Hisashi Koga

Journal of neurosurgery. Spine 1 - 2 2024年9月

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

Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: a cross-species translational study 国際誌

Minae Niwa, Sedona Lockhart, Daniel J. Wood, Kun Yang, Jose Francis-Oliveira, Kyohei Kin, Adeel Ahmed, Gary S. Wand, Shin-ichi Kano, Jennifer L. Payne, Akira Sawa

Nature Mental Health 2 ( 5 ) 593 - 604 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans. Adolescent social isolation prolonged glucocorticoid elevation, leading to long-lasting postpartum behavioral changes in female mice. These changes were unresponsive to current PPD treatments but improved with post-delivery glucocorticoid receptor antagonist treatment. Childhood/adolescent stress significantly impacted HPA axis dysregulation and PPD in human females. Repurposing glucocorticoid receptor antagonists for some cases of treatment-resistant PPD may be considered.

DOI： 10.1038/s44220-024-00217-1

[Initial Medical Care for Spinal Injury].

Susumu Sasada, Kyohei Kin, Takao Yasuhara

No shinkei geka. Neurological surgery 51 ( 6 ) 1051 - 1061 2023年11月

Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke. 国際誌

Takayuki Nagase, Kyohei Kin, Takao Yasuhara

Biomedicines 11 ( 10 ) 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation.

DOI： 10.3390/biomedicines11102773

Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway

Kyohei Kin, Jose Francis-Oliveira, Shin-ichi Kano, Minae Niwa

Nature Communications 2023年1月

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

Satoshi Kawauchi, Takao Yasuhara, Kyohei Kin, Satoru Yabuno, Chiaki Sugahara, Takayuki Nagase, Kakeru Hosomoto, Yosuke Okazaki, Yousuke Tomita, Michiari Umakoshi, Tatsuya Sasaki, Masahiro Kameda, Cesario V Borlongan, Isao Date

CNS neuroscience & therapeutics 28 ( 12 ) 1974 - 1985 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke. METHODS: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed. RESULTS: In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups. CONCLUSION: SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke.

DOI： 10.1111/cns.13947

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

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

Syringo-peritoneal Shunt for Syringomyelia Due to Extensive Adhesive Arachnoiditis: A Case Report.

Kyohei Kin, Takao Yasuhara, Atsuhiko Toyoshima, Isao Date

NMC case report journal 8 ( 1 ) 419 - 425 2021年

記述言語：英語

Adhesive arachnoiditis (AA) is a chronic inflammation inside the dura and remains one of the most challenging diseases. We describe a case of treatment-resistant extensive AA that offers insight into surgical treatment selection. The patient had a 2-year history of progressive spastic gait and was diagnosed with syringomyelia caused by extensive AA. Although syringe-subarachnoid and subarachnoid-subarachnoid shunting resulted in recurrence within a short period, syringo- peritoneal shunting improved the symptoms and there was no recurrence. This case suggests that syringo-peritoneal cerebrospinal fluid (CSF) shunt drainage, which has previously been considered a further step, may be a first-surgery option for extensive AA.

DOI： 10.2176/nmccrj.cr.2020-0228

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

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.

DOI： 10.3390/ijms21114137

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 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. 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

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

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

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

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

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

Kyohei Kin, Takao Yasuhara, Masahiro Kameda, Isao Date

International journal of molecular sciences 20 ( 21 ) 2019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) 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.

DOI： 10.3390/ijms20215402

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

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

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

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

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

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

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

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

Encapsulated stem cells ameliorate depressive-like behavior via growth factor secretion 査読

kyohei kin

Brain Circulation 4 ( 3 ) 128 - 132 2018年7月

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

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 - e398 2018年5月

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

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

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

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

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. 査読国際誌

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

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

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

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

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

The Usefulness of CT-Diffusion Weighted Image Mismatch in Patients with Mild to Moderate Traumatic Brain Injury.

Kyohei Kin, Yasuhiro Ono, Takeshi Fujimori, Satoshi Kuramoto, Atsushi Katsumata, Yuji Goda, Masamitsu Kawauchi

Acta medica Okayama 70 ( 4 ) 237 - 42 2016年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Traumatic brain injury (TBI) has a complex and heterogeneous pathology. It is frequently difficult to predict the neurological deterioration of patients with TBI, and unpredictable change may occur even when TBI is mild to moderate. When computed tomography (CT) findings are considered to be inconsistent with the traumatic origin or with the neurological deterioration of patients observed on admission, magnetic resonance imaging (MRI) is employed based on the standards of our ethical committee. In this retrospective study, we compared CT and diffusion weighted imaging (DWI) of patients with mild to moderate TBI in the very acute phase. When the high-intensity lesions on DWI are larger than the high-density lesions on CT images, we defined the imaging finding as a 'CT-DWI mismatch'. Between January 2010 and December 2013, 92 patients were inspected using both CT and MRI at admission, and we detected a CT-DWI mismatch in 35 patients. CT-DWI mismatch was 92.6% (95% confidence interval 79.8-97.9) sensitive and 84.6% (95% confidence interval 79.3-86.3) specific for the prediction of enlargement of the hemorrhagic lesions on repeat CT. CT-DWI mismatch is considered to be useful as one of the predictors of the enlargement of hemorrhagic lesions in patients with mild to moderate TBI.

脳神経外傷のBasic Research リハビリテーションが神経保護・神経新生に与える影響

安原隆雄, 田尻直輝, 亀田雅博, 大熊佑, 豊嶋敦彦, 竹内勇人, 守本純, 金恭平, 上利崇, 菱川朋人, 伊達勲

日本脳神経外傷学会プログラム・抄録集 39回 71 - 71 2016年2月

[A Case of Transorbital Penetrating Brain Injury Caused by a Steel Wire Entirely Embedded in the Brain Parenchyma]. 査読

Kyohei Kin, Yasuhiro Ono, Takeshi Fujimori, Satoshi Kuramoto, Atsushi Katsumata, Yuji Goda, Masamitsu Kawauchi

No shinkei geka. Neurological surgery 43 ( 10 ) 921 - 6 2015年10月

[A case of intracranial primary leptomeningeal lymphoma]. 査読

Kyohei Kin, Yasuhiro Ono, Yoshio Hisamatsu, Satoshi Kuramoto, Atsushi Katsumata, Hideyuki Yoshida, Masamitsu Kawauchi, Satoko Nakamura

No shinkei geka. Neurological surgery 42 ( 3 ) 233 - 9 2014年3月

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

経動脈的および経静脈的根治的塞栓術を行ったKlippel-Trenaunay-Weber症候群に合併する脊髄辺縁部動静脈瘻の1例

金恭平, 徳永浩司, 春間純, 菱川朋人, 眞鍋博明, 三好康之, 杉生憲志, 伊達勲

JNET: Journal of Neuroendovascular Therapy 6 ( 5 ) 417 - 417 2012年11月

BDNF-secreting capsule exerts neuroprotective effects on epilepsy model of rats 査読

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 - 289 2011年1月

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