Faculty Profiles - MORIHARA Ryuuta

Papers - MORIHARA Ryuuta

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Human Cord Blood-Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model. Reviewed International journal

Hongming Sun, Ryuta Morihara, Tian Feng, Zhihong Bian, Haibo Yu, Xiao Hu, Xinran Hu, Yuting Bian, Ryo Sasaki, Yusuke Fukui, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Koji Abe, Toru Yamashita

Cell transplantation 32 9636897231193069 - 9636897231193069 2023

Language：English Publishing type：Research paper (scientific journal)

Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.

DOI： 10.1177/09636897231193069

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Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial. Reviewed International journal

Toru Yamashita, Yumiko Nakano, Ryo Sasaki, Koh Tadokoro, Yoshio Omote, Taijun Yunoki, Yuko Kawahara, Namiko Matsumoto, Yuki Taira, Chika Matsuoka, Ryuta Morihara, Koji Abe

Cell transplantation 32 9636897231214370 - 9636897231214370 2023

Language：English Publishing type：Research paper (scientific journal)

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.

DOI： 10.1177/09636897231214370

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Tocovid Attenuated Oxidative Stress and Cognitive Decline by Inhibiting Amyloid-β-Induced NOX2 Activation in Alzheimer's Disease Mice. International journal

Zhihong Bian, Haibo Yu, Xinran Hu, Yuting Bian, Hongming Sun, Koh Tadokoro, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Yusuke Fukui, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 2022.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: NADPH oxidase 2 (NOX2) is an important source of reactive oxygen species (ROS). Activated NOX2 may contribute to Alzheimer's disease (AD). Our previous studies showed that a novel vitamin E mixture, Tocovid, had potential neuroprotective effects in a stroke mice model and an AD cell model. OBJECTIVE: The aim of this study was two-fold: to assess whether long-term Tocovid treatment can regulate NOX2, and the therapeutic effects of long-term administration of Tocovid to an AD mice model. METHODS: Therapeutic effects of long-term administration of Tocovid (200 mg/kg /day) on an Aβ-overexpressed transgenic AD mice model (APP23, n = 8) was investigated. The therapeutic effect of Tocovid in 16-month-old mice compared with the no-treatment APP23 group (n = 9) was assessed. RESULTS: Tocovid treatment strongly improved motor and memory deficits of APP23 mice by attenuating NOX2 expression, oxidative stress, neuroinflammation, neurovascular unit dysfunction, synaptic alteration, and Aβ deposition after 16 months. CONCLUSION: These findings suggest that NOX2 is a potential target in AD pathology. Long-term administration of Tocovid may be a promising candidate for AD treatment.

DOI： 10.3233/JAD-220761

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Novel <scp> ABCD1 </scp> mutation detected in a symptomatic female carrier of adrenoleukodystrophy

Yumiko Nakano, Yuki Taira, Ryo Sasaki, Koh Tadokoro, Taijun Yunoki, Emi Nomura, Yusuke Fukui, Mami Takemoto, Ryuta Morihara, Nobuyuki Shimozawa, Toru Yamashita

Neurology and Clinical Neuroscience 2022.10

Protective and anti-oxidative effects of curcumin and resveratrol on Aβ-oligomer-induced damage in the SH-SY5Y cell line. International journal

Haibo Yu, Toru Yamashita, Xiao Hu, Zhihong Bian, Xinrang Hu, Tian Feng, Koh Tadokoro, Ryuta Morihara, Koji Abe

Journal of the neurological sciences 441 120356 - 120356 2022.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER

Alzheimer's disease (AD) is a degenerative disorder characterized by the loss of synapses and neurons in the brain, and results in the accumulation of amyloid-based neurotic plaques. Amyloid-β oligomers (AβO) are widely accepted as the main neurotoxin that induces oxidative stress and neuronal loss in AD. In this study, an oxidative stress model of the neuroblastoma SH-SY5Y cell line exposed to AβO was established to simulate an AD cell model. Exposure to AβO significantly reduced the viability of cultured SH-SY5Y cells (p < 0.05) and significantly increased intracellular reactive oxygen species (ROS) (p < 0.01). AβO exposure also induced oxidative stress in SH-SY5Y cells. Furthermore, AβO significantly increased the level of hyperphosphorylation of tau at sites T181 and T205 in SH-SY5Y cells (p < 0.01). Using edaravone, a free radical scavenger with neuroprotective properties, as the control, the possible protective and anti-oxidative effects of curcumin (40 μM) and resveratrol (20 μM) were evaluated. The results suggest that curcumin and resveratrol decreased ROS generation, attenuated oxidative stress, inhibited tau hyperphosphorylation, and protected SH-SY5Y cells from AβO damage. Both curcumin and resveratrol are promising supplements or medicine as therapeutic agents for the treatment of AD.

DOI： 10.1016/j.jns.2022.120356

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視線計測計Gazefinderを用いた認知症診断の可能性

田所功, 福井裕介, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 小坂田陽介, 松本菜見子, 佐々木諒, 武本麻美, 菱川望, 森原隆太, 阿部康二, 山下徹

臨床神経学 62 ( Suppl. ) S323 - S323 2022.10

AβオリゴマーによるSH-SY5Y細胞傷害に対するクルクミンとレスベラトロールの保護効果(Protective effects of curcumin and resveratrol on Aβ-oligomer-induced damage in the SH-SY5Y cell)

于海波, 山下徹, 胡梟, 卞之宏, 胡欣冉, 馮田, 田所功, 森原隆太, 阿部康二

脳循環代謝 34 ( 1 ) 159 - 159 2022.10

脳低灌流を伴うアルツハイマー病モデルマウスにおけるプラズマローゲンの有効性(Efficiency of Plasmalogen in a Mouse Model of Alzheimer's Disease with Cerebral Hypoperfusion)

Zhai Yun, Feng Tian, 胡欣冉, 福井裕介, 卞之宏, Bian Yuting, 孫洪銘, 武本麻美, 柚木太淳, 中野由美子, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 160 - 160 2022.10

パーキンソン病におけるMRgFUSによる片側視床または淡蒼球破壊術の治療成績検討

小坂田陽介, 平林秀裕, 森原隆太, 山下徹, 阿部康二, 久我純弘, 大西英之

臨床神経学 62 ( Suppl. ) S206 - S206 2022.10

RivaroxabanはADマウスのPAR-1/PAR-2阻害によりアミロイド病態と神経炎症を抑制する(Rivaroxaban attenuated amyloid pathology and neuroinflammation by inhibiting PAR-1/PAR-2 in AD mice)

Bian Zhihong, Liu Xia, Yu Haibo, Hu Xinran, Bian Yuting, Sun Hongming, 田所功, 武本麻美, 柚木太淳, 中野由美子, 福井裕介, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 158 - 158 2022.10

視線計測計を用いた認知機能障害の早期スクリーニング

福井裕介, 田所功, 野村恵美, 涌谷陽介, 高尾芳樹, 東靖人, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 阿部康二, 山下徹

脳循環代謝 34 ( 1 ) 150 - 150 2022.10

脳梗塞モデルマウスにおけるカルノシンの抗酸化作用と抗炎症作用(Anti-oxidative and the anti-inflammatory response of carnosine in a mice stroke model)

胡欣冉, 阿部康二, 福井裕介, 中野由美子, 柚木太淳, 武本麻美, 森原隆太, 山下徹

脳循環代謝 34 ( 1 ) 153 - 153 2022.10

慢性進行性の頭頂葉性運動失調症を認めた家族性及び孤発性の7症例

森原隆太, 山下徹, 池内健, 北口正孝, 阿部康二

脳循環代謝 34 ( 1 ) 151 - 151 2022.10

髄液検体から診断に至った再発性の抗MOG抗体関連疾患の2症例

中野由美子, 佐々木諒, 中田有美, 田所功, 柚木太淳, 野村恵美, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

腺性自己免疫症候群3型に抗MOG抗体関連急性脊髄炎を合併した一例

柚木太淳, 中野由美子, 中田有美, 佐々木諒, 田所功, 武本麻美, 森原隆太, 山下徹

臨床神経学 62 ( 10 ) 824 - 824 2022.10

Japanese case of Charcot-Marie-Tooth disease type 2Z with severe retinitis pigmentosa

Emi Nomura, Koh Tadokoro, Ryo Sasaki, Yumi Nakata, Yumiko Nakano, Taijun Yunoki, Mami Takemoto, Ryuta Morihara, Masahiro Ando, Hiroshi Takashima, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 10 ( 5 ) 266 - 268 2022.9

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Charcot-Marie-Tooth disease type 2Z (CMT2Z) shows highly variable clinical features. We report the first Japanese CMT2Z patient with a c.754C>T (p.R252W) substitution of the MORC2 gene, complicating severe retinitis pigmentosa. The MORC2 mutants were involved in a decrease in cell survival through induction of apoptosis. Thus, the MORC2 mutation might be involved in the degeneration of photoreceptors and the development of retinitis pigmentosa.

DOI： 10.1111/ncn3.12660

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A case of successful renal transplantation of Charcot-Marie-Tooth disease associated with FSGS due to mutation of the INF2 gene

Chika Matsuoka, Yuki Taira, Ryo Sasaki, Namiko Matsumoto, Koh Tadokoro, Emi Nomura, Yuko Kawahara, Mami Takemoto, Ryuta Morihara, Akihiro Hashiguchi, Hiroshi Takashima, Hidemi Takeuchi, Motoo Araki, Koji Abe, Toru Yamashita

Neurology and Clinical Neuroscience 10 ( 5 ) 252 - 254 2022.9

Publishing type：Research paper (scientific journal)

Focal and segmental areas of glomerular sclerosis (FSGS) have various subcategories. Here, we report on a 35-year-old man who suffered from Charcot-Marie-Tooth disease (CMT) with FSGS carrying the INF2 mutation (c.206 T > C, p.L69P). The INF2 mutation might cause abnormal actin filaments of the podocytes and Schwann cells, leading to CMT associated with FSGS. He successfully underwent living donor kidney transplantation from a mother with a normal INF2 gene without any serious adverse events. Following genetic testing, the identification of the INF2 mutation allows a recipient to reduce the use of immunosuppressive drugs. Genetic testing may provide a treatment plan for kidney transplantation.

DOI： 10.1111/ncn3.12651

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Efficacy and safety of spot heating and ultrasound irradiation on in vitro and in vivo thrombolysis models. International journal

Ryuta Morihara, Toru Yamashita, Yosuke Osakada, Tian Feng, Xinran Hu, Yusuke Fukui, Koh Tadokoro, Mami Takemoto, Koji Abe

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 42 ( 7 ) 1322 - 1334 2022.7

Language：English Publishing type：Research paper (scientific journal)

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.

DOI： 10.1177/0271678X221079127

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A Japanese case of successful surgical resection of cerebral cavernous malformations with a CCM2 mutation

Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yumiko Nakano, Taijun Yunoki, Ryuta Morihara, Tatsuya Sasaki, Hiroyuki Akagawa, Koji Abe, Toru Yamashita

NEUROLOGY AND CLINICAL NEUROSCIENCE 2022.6

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

Cerebral cavernous malformations (CCMs) are congenital abnormalities of cerebral vessels. Surgical resection is rarely considered for the control of epilepsy in a first seizure patient with vascular malformation. In contrast, lesions that produce repetitive or progressive symptoms should be considered for surgical resection as treatment. Herein, we report a Japanese patient with a CCM2 mutation, c.609G>A (p.K203K) substitution, who showed drug-resistant epilepsy and dramatic improvement after surgical resection.

DOI： 10.1111/ncn3.12649

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Clinical and Pathological Benefits of Scallop-Derived Plasmalogen in a Novel Mouse Model of Alzheimer's Disease with Chronic Cerebral Hypoperfusion. International journal

Tian Feng, Xinran Hu, Yusuke Fukui, Zhihong Bian, Yuting Bian, Hongming Sun, Mami Takemoto, Taijun Yunoki, Yumiko Nakano, Ryuta Morihara, Koji Abe, Toru Yamashita

Journal of Alzheimer's disease : JAD 86 ( 4 ) 1973 - 1982 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer's disease (AD) patients. OBJECTIVE: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20-30% among the dementia society, were still elusive. METHODS: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. RESULTS: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-β pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. CONCLUSION: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.

DOI： 10.3233/JAD-215246

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Papers - MORIHARA Ryuuta