研究者詳細 - 小野寺　理

論文 - 小野寺　理

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Strategies to prevent hemorrhagic transformation after reperfusion therapies for acute ischemic stroke: A literature review. 国際誌

Yutaka Otsu, Masaki Namekawa, Masafumi Toriyabe, Itaru Ninomiya, Masahiro Hatakeyama, Masahiro Uemura, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

Journal of the neurological sciences 419 117217 - 117217 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Reperfusion therapies by tissue plasminogen activator (tPA) and mechanical thrombectomy (MT) have ushered in a new era in the treatment of acute ischemic stroke (AIS). However, reperfusion therapy-related HT remains an enigma. AIM: To provide a comprehensive review focused on emerging concepts of stroke and therapeutic strategies, including the use of protective agents to prevent HT after reperfusion therapies for AIS. METHODS: A literature review was performed using PubMed and the ClinicalTrials.gov database. RESULTS: Risk of HT increases with delayed initiation of tPA treatment, higher baseline glucose level, age, stroke severity, episode of transient ischemic attack within 7 days of stroke onset, and hypertension. At a molecular level, HT that develops after thrombolysis is thought to be caused by reactive oxygen species, inflammation, remodeling factor-mediated effects, and tPA toxicity. Modulation of these pathophysiological mechanisms could be a therapeutic strategy to prevent HT after tPA treatment. Clinical mechanisms underlying HT after MT are thought to involve smoking, a low Alberta Stroke Program Early CT Score, use of general anesthesia, unfavorable collaterals, and thromboembolic migration. However, the molecular mechanisms are yet to be fully investigated. Clinical trials with MT and protective agents have also been planned and good outcomes are expected. CONCLUSION: To fully utilize the easily accessible drug-tPA-and the high recanalization rate of MT, it is important to reduce bleeding complications after recanalization. A future study direction could be to investigate the recovery of neurological function by combining reperfusion therapies with cell therapies and/or use of pleiotropic protective agents.

DOI： 10.1016/j.jns.2020.117217

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Progressive supranuclear palsy: Neuropathology of patients with a short disease duration due to unexpected death 国際誌

Lu Zhang, Yasuko Toyoshima, Akari Takeshima, Hiroshi Shimizu, Itsuro Tomita, Osamu Onodera, Hitoshi Takahashi, Akiyoshi Kakita

NEUROPATHOLOGY 41 ( 3 ) 174 - 182 2020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：WILEY

Progressive supranuclear palsy (PSP) presents with a wide variety of signs/symptoms, making early initial diagnosis difficult. We investigated the clinical and neuropathological features of five patients with autopsy-proven PSP of short duration, ranging from 11 to 41 months (average, 26.2 months) due to unexpected death, focusing particularly on the distribution and severity of neuronal loss as well as neuronal and glial tau pathology in the affected brain. Clinical features were studied retrospectively through careful review of the medical records, and neuropathological examinations were carried out, along with tau immunohistochemistry using a monoclonal antibody AT8. These patients were diagnosed as having probable PSP (n = 4) and suggestive PSP (n = 1), respectively. In all cases, neuronal loss was evident in the substantia nigra, subthalamic nucleus, globus pallidus, and locus ceruleus. AT8-identified tau lesions, that is, pretangles/neurofibrillary tangles (PTs/NFTs), tufted astrocytes (TAs), and coiled bodies/neuropil threads (CBs/NTs), were distributed widely in the brain regions, especially in patients with longer disease duration. All cases showed variation in the regional tau burden among PTs/NFTs, TAs, and CBs/NTs. There was also a tendency for tau deposition to be more predominant in neuronal cells in the brainstem and cerebellum and in glial cells in the cerebral cortex and subcortical gray matter. These findings suggest that in PSP, the initial signs/symptoms are associated with degeneration and subsequent death of neurons with pathological tau deposition, and that the tau deposition in neuronal cells is independent of that in glial cells.

DOI： 10.1111/neup.12707

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Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island. 国際誌

Kei Takamisawa, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kazutoshi Nakamura, Osamu Onodera, Takeshi Momotsu, Naoto Endo, Kenji Sato, Ichiei Narita, Hiromasa Yoshie, Koichi Tabeta

Heliyon 6 ( 11 ) e05531 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. Methods: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. Results: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. Conclusions: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

DOI： 10.1016/j.heliyon.2020.e05531

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筋萎縮性側索硬化症の確定診断までの時間に与える、初診科、発症部位の検討

大津裕, 小池佑佳, 石原智彦, 小野寺理

臨床神経学 60 ( Suppl. ) S380 - S380 2020年11月

神経疾患・精神疾患の鑑別における血漿炎症性サイトカインの有用性

樋口陽, 春日健作, 徳武孝允, 宮下哲典, 茂木崇治, 福井直樹, 横山裕一, 染矢俊幸, 小野寺理, 池内健

臨床神経学 60 ( Suppl. ) S377 - S377 2020年11月

多系統萎縮症における脳脊髄液中NG2とα-シヌクレインの検討

徳武孝允, 春日健作, 月江珠緒, 樋口陽, 下畑享良, 小野寺理, 池内健

臨床神経学 60 ( Suppl. ) S433 - S433 2020年11月

CADASIL原因遺伝子NOTCH3のシステイン非関連variant p.Val237Metの病的意義の検討

水田依久子, 加納裕也, 植田明彦, 野崎洋明, 櫻井圭太, 小野寺理, 安東由喜雄, 湯浅浩之, 水野敏樹

臨床神経学 60 ( Suppl. ) S421 - S421 2020年11月

日本におけるSOD1遺伝子変異陽性筋萎縮性側索硬化症患者の臨床的特徴

中村亮一, 熱田直樹, 藤内玄規, 林直毅, 勝野雅央, 和泉唯信, 金井数明, 服部信孝, 谷口彰, 森田光哉, 狩野修, 澁谷和幹, 桑原聡, 鈴木直輝, 青木正志, 阿部康二, 石原智彦, 小野寺理, 梶龍兒, 祖父江元

臨床神経学 60 ( Suppl. ) S381 - S381 2020年11月

CADASIL原因遺伝子NOTCH3のシステイン非関連variant p.Val237Metの病的意義の検討

水田依久子, 加納裕也, 植田明彦, 野崎洋明, 櫻井圭太, 小野寺理, 安東由喜雄, 湯浅浩之, 水野敏樹

臨床神経学 60 ( Suppl. ) S421 - S421 2020年11月

ALS剖検例に関するテキストマイニングとエキソーム分析を用いたALSの新規候補遺伝子の探索(Search for new candidate genes for ALS by textmining and exome analysis of autopsy cases)

Hatano Yuya, Ishihara Tomohiko, Yokoseki Akio, Tada Mari, Kakita Akiyoshi, Okuda Shujiro, Onodera Osamu

臨床神経学 60 ( Suppl. ) S324 - S324 2020年11月

散発性ALSの137症例における剖検物のエキソーム分析(Exome analysis in 137 autopsied sporadic ALS cases)

Ishihara Tomohiko, Hatano Yuya, Yokoseki Akio, Tada Mari, Nakajima Takashi, Koike Ryoko, Kakita Akiyoshi, Onodera Osamu

臨床神経学 60 ( Suppl. ) S309 - S309 2020年11月

[Cell Therapy Using Peripheral Mononuclear Cells Preconditioned by Oxygen-Glucose Deprivation for Ischemic Stroke].

Masahiro Hatakeyama, Itaru Ninomiya, Osamu Onodera, Takayoshi Shimohata, Masato Kanazawa

Brain and nerve = Shinkei kenkyu no shinpo 72 ( 10 ) 1097 - 1103 2020年10月

記述言語：日本語掲載種別：研究論文（学術雑誌）

Many studies in recent years have reported cell therapies using embryonic stem cells, induced pluripotent stem cells, and bone marrow-derived mononuclear cells for cerebral ischemia. However, obtaining these cells is challenging, and these cell therapies require complicated procedures to prepare cells for administration. Notably, peripheral blood mononuclear cells (PBMCs) are a useful cell source for clinical applications because cell collection is easier. In this review, we report the therapeutic effects of PBMCs preconditioned by oxygen-glucose deprivation (OGD-PBMCs) on cerebral ischemia. Cell therapies using tissue-protective OGD-PBMCs might be a simple and ideal therapeutic strategy against ischemic stroke.

DOI： 10.11477/mf.1416201655

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本邦におけるCADASILの全国調査と多施設データベースの構築

新堂晃大, 田部井賢一, 谷口彰, 小野寺理, 安東由喜雄, 卜部貴夫, 北川一夫, 羽生春夫, 平野照之, 脇田英明, 福山秀直, 鍵村達夫, 宮本恵宏, 竹上未紗, 水田依久子, 猪原匡史, 水野敏樹, 冨本秀和

Dementia Japan 34 ( 4 ) 491 - 491 2020年10月

本邦におけるCADASILの全国調査と多施設データベースの構築

Dementia Japan 34 ( 4 ) 491 - 491 2020年10月

実は見逃されている血管性認知症の危険因子

山下徹, 野崎洋明, 涌谷陽介, 田所功, 野村恵美, 菱川望, 武本麻美, 太田康之, 小野寺理, 阿部康二

Dementia Japan 34 ( 4 ) 493 - 493 2020年10月

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis. 国際誌

Ryoichi Nakamura, Kazuharu Misawa, Genki Tohnai, Masahiro Nakatochi, Sho Furuhashi, Naoki Atsuta, Naoki Hayashi, Daichi Yokoi, Hazuki Watanabe, Hirohisa Watanabe, Masahisa Katsuno, Yuishin Izumi, Kazuaki Kanai, Nobutaka Hattori, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Kazumoto Shibuya, Satoshi Kuwabara, Naoki Suzuki, Masashi Aoki, Yasuyuki Ohta, Toru Yamashita, Koji Abe, Rina Hashimoto, Ikuko Aiba, Koichi Okamoto, Kouichi Mizoguchi, Kazuko Hasegawa, Yohei Okada, Tomohiko Ishihara, Osamu Onodera, Kenji Nakashima, Ryuji Kaji, Yoichiro Kamatani, Shiro Ikegawa, Yukihide Momozawa, Michiaki Kubo, Noriko Ishida, Naoko Minegishi, Masao Nagasaki, Gen Sobue

Communications biology 3 ( 1 ) 526 - 526 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10-8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10-4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10-11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.

DOI： 10.1038/s42003-020-01251-2

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クエチアピン単剤化により精神症状と運動症状が改善したハンチントン病による認知症の1例

宮下真子, 渡部雄一郎, 本郷祥子, 小池直人, 佐治越爾, 深石翔, 三上剛明, 小野寺理, 染矢俊幸

精神神経学雑誌 ( 2020特別号 ) S313 - S313 2020年9月

Cell Therapies under Clinical Trials and Polarized Cell Therapies in Pre-Clinical Studies to Treat Ischemic Stroke and Neurological Diseases: A Literature Review. 査読国際誌

Masahiro Hatakeyama, Itaru Ninomiya, Yutaka Otsu, Kaoru Omae, Yasuko Kimura, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata, Masato Kanazawa

International journal of molecular sciences 21 ( 17 ) 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy; they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

DOI： 10.3390/ijms21176194

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Novel CHP1 mutation in autosomal-recessive cerebellar ataxia: autopsy features of two siblings. 査読国際誌

Rie Saito, Norikazu Hara, Mari Tada, Yoshiaki Honma, Akinori Miyashita, Osamu Onodera, Takeshi Ikeuchi, Akiyoshi Kakita

Acta neuropathologica communications 8 ( 1 ) 134 - 134 2020年8月

[Dural arteriovenous fistula causing complex visual hallucinations without an anopsia]. 査読

Shingo Koide, Masahiro Hatakeyama, Masahiro Uemura, Bumpei Kikuchi, Hitoshi Hasegawa, Osamu Onodera

Rinsho shinkeigaku = Clinical neurology 60 ( 6 ) 425 - 428 2020年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）

We report the case of a 76-year-old woman who presented with recurrent episodes of complex visual hallucinations in her right visual field without an anopsia. The electroencephalogram showed sharp transients in the left parietotemporal region with phase reversals at T5 and P3. FLAIR MRI revealed hyperintense lesions in the left temporo-occipital lobe, located mainly in the left inferior temporal lobe. Cerebral angiography revealed an arteriovenous shunt from the left occipital artery to the left transverse sinus with cortical venous reflux. The complex visual hallucinations were resolved after transarterial embolization. We therefore hypothesize that this patient's complex visual hallucinations were caused by epileptic seizures or changes in cortical blood flow caused by the cortical venous reflux from the arteriovenous fistula. In general, epileptic hallucinations expand into the bilateral visual field. We reveal that in rare cases, complex visual hallucinations can also be limited to the unilateral visual field without an anopsia. Additionally, we reveal that a dural arteriovenous fistula can cause visual hallucinations without hemianopia.

DOI： 10.5692/clinicalneurol.60.cn-001371

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