Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10286-021-00826-1

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Other Link： https://link.springer.com/article/10.1007/s10286-021-00826-1/fulltext.html

Language：Japanese   Publisher：(一社)日本神経学会  

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.clineuro.2021.106496

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Authorship：Lead author   Language：Japanese   Publisher：(一社)日本内科学会  

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

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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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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

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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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞近年,脳梗塞に対する細胞療法の研究が盛んに行われているが,既存の細胞療法は,投与細胞の採取や調整に複雑な手技を要するため,一般臨床への普及が難しい。われわれは,末梢血単核球に,低酸素低糖刺激という簡便な刺激を加えることにより,脳梗塞に対して治療効果のある細胞を調整できることを証明した。本稿では,われわれの開発した技術と今後の展望について概説する。

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J04871&link_issn=&doc_id=20201012210017&doc_link_id=40022380199&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F40022380199&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Language：Japanese   Publisher：(一社)日本臨床神経生理学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

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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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞75歳,女性.当科初診の2ヵ月前から足趾の冷感,暗紫色調の変化を自覚するようになった.皮疹出現の1ヵ月後に意識障害が生じ,当院に緊急入院した.頭部画像検査で異常所見は認めず,意識障害の原因は不明であった.皮疹に関して当科を紹介され受診した.足趾に凍瘡様皮疹,頬部や耳介部に浸潤の触れる角化性紅斑を認めた.左頬部紅斑の病理組織検査で,表皮真皮境界部の液状変性および真皮付属器周囲にリンパ球を主体とした炎症細胞の浸潤を認めた.凍瘡状ループスに加え汎血球減少,低補体血症,抗核抗体陽性がみられたことから,neuropsychiatric systemic lupus erythematosus(NPSLE)を伴った全身性エリテマトーデスと診断した.意識障害はステロイド全身投与により改善した.エリテマトーデスを疑う皮疹をもつ原因不明の意識障害患者を診察した際,NPSLEを鑑別に挙げ全身を診察することが重要である.

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01559&link_issn=&doc_id=20200603050006&doc_link_id=10.11477%2Fmf.1412206068&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1412206068&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medknow  

Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke. Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit. In this mini-review, we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia. Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery. Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery. First, new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling. Second, blood vessels are thought to enhance neurogenesis in three stages: 1) Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals, 2) microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen, nutrients, and soluble factors as well as serving as a scaffold for migration, and 3) oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons. Thus, the regions of angiogenesis and surrounding tissue may be coupled, representing novel treatment targets.

DOI： 10.4103/1673-5374.264442

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Authorship：Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Societas Neurologica Japonica  

DOI： 10.5692/clinicalneurol.60.cn-001371

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β <italic>in vitro</italic>, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia <italic>in vivo</italic>. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both <italic>in vitro</italic> and <italic>in vivo</italic>. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.

DOI： 10.1038/s41598-019-53418-5

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Other Link： http://www.nature.com/articles/s41598-019-53418-5

Language：Japanese   Publisher：(一社)日本神経学会  

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：Movement Disorder Society of Japan (MDSJ)  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：Movement Disorder Society of Japan (MDSJ)  

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Language：Japanese   Publisher：(一社)日本神経治療学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

OBJECTIVE:To determine predictors of cognitive impairment and frontal dysfunction in patients with multiple system atrophy (MSA). METHODS:We recruited 59 patients with MSA and determined the predictors of a decline in the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores. RESULTS:The MMSE scores negatively correlated with disease duration, Unified MSA Rating Scale (UMSARS) part 1 and 4 scores, and residual urine volume, and positively correlated with the coefficient of variation of electrocardiographic RR intervals. The FAB scores negatively correlated with the UMSARS part 2 score, periventricular hyperintensity grade, and deep white matter hyperintense signal grade. A significant predictor of rapidly progressive cognitive impairment was a high residual urine volume. CONCLUSIONS:Impairment of global cognitive function correlates with the long-term disease duration, global disability due to the disease, and autonomic dysfunction, whereas frontal dysfunction correlates with motor function and degeneration of cerebral white matter.

DOI： 10.1016/j.jns.2018.03.017

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Language：Japanese   Publisher：(一社)日本脳循環代謝学会  

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke. Microglia and monocytes/macrophages polarize to the classic pro-inflammatory type (M1-like) or alternative protective type (M2-like) by optimal condition. Cell-based therapies using M2-like microglia and monocytes/macrophages might be protective therapeutic strategies against stroke for three reasons. First, M2-like microglia and monocytes/monocytes secrete protective remodeling factors, thus prompting neuronal network recovery via tissue (including neuronal) and vascular remodeling. Second, these cells could migrate to the injured hemisphere through the blood-brain barrier or choroid-plexus. Third, these cells could mitigate the extent of inflammation-induced injuries by suitable timing of therapeutic intervention. Although future translational studies are required, M2-like microglia and monocytes/macrophages therapies are attractive for managing stroke based on their protective functions.

DOI： 10.3390/ijms18102135

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Cell-therapies that invoke pleiotropic mechanisms may facilitate functional recovery in stroke patients. We hypothesized that a cell therapy using microglia preconditioned by optimal oxygen-glucose deprivation (OGD) is a therapeutic strategy for ischemic stroke because optimal ischemia induces anti-inflammatory M2 microglia. We first delineated changes in angiogenesis and axonal outgrowth in the ischemic cortex using rats. We found that slight angiogenesis without axonal outgrowth were activated at the border area within the ischemic core from 7 to 14 days after ischemia. Next, we demonstrated that administration of primary microglia preconditioned by 18 hours of OGD at 7 days prompted functional recovery at 28 days after focal cerebral ischemia compared to control therapies by marked secretion of remodelling factors such as vascular endothelial growth factor, matrix metalloproteinase-9, and transforming growth factor-β polarized to M2 microglia in vitro/vivo. In conclusion, intravascular administration of M2 microglia preconditioned by optimal OGD may be a novel therapeutic strategy against ischemic stroke.

DOI： 10.1038/srep42582

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Other Link： http://www.nature.com/articles/srep42582.pdf

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

DOI： 10.1111/ncn3.12065

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jns.2015.06.057

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Language：Japanese   Publisher：(株)医学書院  

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Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J04871&link_issn=&doc_id=20140718240019&doc_link_id=10.11477%2Fmf.1416101849&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1416101849&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Societas Neurologica Japonica  

Pyogenic ventriculitis is an uncommon and potentially fatal central nervous system infection. Delayed treatment due to non specific clinical symptoms may lead to an unfavorable outcome. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of pyogenic ventriculitis. We describe two patients with pyogenic ventriculitis presenting with a pathognomonic MRI finding. The first patient, a 77-year-old female, developed high fever and consciousness disturbance. MR images revealed hyperintense lesions with a fluid-fluid level in the bilateral lateral ventricles on diffusion-weighted images (DWIs) and hypointense lesions on T2-weighted images (T2WIs). MR images also revealed findings of left otitis media. The second patient, a 63-year-old male, who had a past history of multiple myeloma and had received chemotherapy, developed high fever and left hemiparesis. MR images revealed a hyperintense lesion with a fluid-fluid level in the right lateral ventricle on DWIs and a hypointense lesion on T2WIs, multiple ring-enhancing lesions on gadolinium enhanced T1-weighted images, and pontine infarction on DWIs. Chest computed tomography revealed an infiltrative shadow in the lower lobe of the left lung. On the basis of MRI findings, both patients were diagnosed as having pyogenic ventriculitis and were administered high-dose meropenem intravenously. The second patient was also administered sulfamethoxazole-trimethoprim orally. Intraventricular abnormalities disappeared and the patients achieved complete remission after the antibacterial treatment. Intraventricular hyperintense lesions on DWIs and hypointense ones on T2WIs with a fluid-fluid level is a pathognomonic finding of pyogenic ventriculitis and has not been previously reported in other diseases. Recognition of the characteristic MRI features and initiation of high-dose and appropriate antibiotics in an early stage may lead to a favorable outcome of the disease.

DOI： 10.5692/clinicalneurol.54.732

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Igaku-Shoin Ltd  

Scopus

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：Japanese   Publisher：日本神経心理学会  

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Language：Japanese   Publisher：(一社)日本認知症学会  

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Language：Japanese   Publisher：(株)全日本病院出版会  

神経免疫疾患では、多彩な高次脳機能障害が認められる。そのうち、多発性硬化症(MS)では、長期記憶障害、注意機能障害、情報処理能力の低下、遂行機能障害、視空間認知障害などが認められ、患者の社会活動参加や日常生活において支障となり得る。MSの高次脳機能障害は、一般的なスクリーニング検査では評価が不十分であることが多いため、BRBNなど適切な検査法を用いる必要がある。また、MSの高次脳機能障害は疾患修飾薬の導入により進行が抑制できるため、初期からの治療導入が重要である。また、視神経脊髄炎でも注意機能、情報処理能力、言語性長期記憶に障害が認められる。その他、全身性エリテマトーデス、Sjoegren症候群、ベーチェット病などの自己免疫性疾患、炎症性疾患の神経症状として、高次脳機能障害が認められることがあり、これらの疾患の診療においては注意が必要である。(著者抄録)

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2017375055

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：WILEY  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SAGE PUBLICATIONS INC  

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Language：Japanese   Publisher：日本神経感染症学会  

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Language：Japanese   Publisher：(一社)日本神経学会  

J-GLOBAL

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