Details of a Researcher - Izawa, Yoshikane

Izawa, Yoshikane

写真a

Affiliation: School of Medicine, Department of Internal Medicine (Neurology) （Shinanomachi）

Position: Assistant Professor/Senior Assistant Professor

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Career 【 Display / hide 】

2003.05

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2005.04

慶應義塾大学医学部研修医（内科）
2007.04

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2009.09

慶應義塾大学医学部神経内科
2009.10

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2011.10

慶應義塾大学脳血管障害予防医学寄附講座
2011.11

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2014.10

University of Washington, School of Medicine, Division of Hematology
2014.11

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2018.09

慶應義塾大学医学部神経内科, 助教

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Academic Degrees 【 Display / hide 】

博士（医学） DMSc, Keio University, Dissertation, 2011.10

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Research Keywords 【 Display / hide 】

Neurovsacular unit
脳血管障害　Cerebrovascular disease
血液脳関門　Blood brain barrier

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Papers 【 Display / hide 】

Trends of Antiplatelet Therapy for the Management of Moyamoya Disease in Japan: Results of a Nationwide Survey

Oki K., Katsumata M., Izawa Y., Takahashi S., Suzuki N., Houkin K.

Journal of Stroke and Cerebrovascular Diseases （Journal of Stroke and Cerebrovascular Diseases) 27 （ 12 ） 3605 - 3612 2018.12

ISSN 10523057

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© 2018 National Stroke Association Background: The efficacy and safety of antiplatelet drugs in the treatment of moyamoya disease remain unclear. This study reports results of a nationwide survey conducted in 2016 on the trends of antiplatelet therapy for moyamoya disease in Japan. Methods: Data were obtained through questionnaires related to treatment policies regarding antiplatelet drugs from each specialized stroke management department of 765 hospitals in Japan. Data were also compared between experienced facilities (defined as facilities managing more than 10 cases per year) and those less experienced (not more than 10 cases per year) to determine experts' opinion. Results: Of the 389 departments in 375 hospitals that responded, 330 departments provided medical care for moyamoya disease. Regarding ischemic stroke, numerous departments considered the use of antiplatelet drugs “in principle” (218 departments). After surgery for ischemic moyamoya disease, the use of antiplatelet drugs for a certain period of time was the most popular opinion (74 departments). Regarding asymptomatic moyamoya disease, majority departments reported no use of APDs “in principle” (256 departments). The experienced facilities reported “no use of antiplatelet drugs” more frequently than those less experienced for treating asymptomatic moyamoya disease. In moyamoya disease, aspirin was the most commonly used antiplatelet drugs followed by cilostazol and clopidogrel. Conclusions: This survey revealed details of treatment policies, and the selection of antiplatelet drugs widely varied across facilities. Further prospective studies are necessary to improve the current unclear situation regarding the use of antiplatelet drugs for the management of moyamoya disease.
- Access to Document (DOI)
Neuroprotective Role of Astroglia in Parkinson Disease by Reducing Oxidative Stress Through Dopamine-Induced Activation of Pentose-Phosphate Pathway

Mashima K., Takahashi S., Minami K., Izawa Y., Abe T., Tsukada N., Hishiki T., Suematsu M., Kajimura M., Suzuki N.

ASN Neuro （ASN Neuro) 10 2018.05

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© The Author(s) 2018. Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice. The rates of glucose phosphorylation in astroglia were evaluated using the [ 14 C]deoxyglucose method. PPP activity was measured using [1- 14 C]glucose and [6- 14 C]glucose after acute (60 min) or chronic (15 hr) exposure to dopamine. ROS production was measured using 2′,7′-dichlorodihydrofluorescein diacetate. The involvement of the Kelch-like ECH-associated protein 1 (Keap1) or nuclear factor-erythroid-2-related factor 2 (Nrf2) system was evaluated using Nrf2 gene knockout mice, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction analysis for heme oxygenase-1. Acute exposure to dopamine elicited increases in astroglial glucose consumption with lactate release. PPP activity in astroglia was robustly enhanced independently of Na + -dependent monoamine transporters. In contrast, chronic exposure to dopamine induced moderate increases in PPP activity via the Keap1/Nrf2 system. ROS production from dopamine increased gradually over 12 hr. Dopamine induced neuronal cell damage that was prevented by coculturing with astroglia but not with Nrf2-deficient astroglia. Dopamine-enhanced astroglial PPP activity in both acute and chronic manners may possibly reduce neuronal oxidative stress.
- Access to Document (DOI)
β1-integrin–matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability

Izawa Y., Gu Y., Osada T., Kanazawa M., Hawkins B., Koziol J., Papayannopoulou T., Spatz M., del Zoppo G.

Journal of Cerebral Blood Flow and Metabolism （Journal of Cerebral Blood Flow and Metabolism) 38 （ 4 ） 641 - 658 2018.04

ISSN 0271678X

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© 2017, © The Author(s) 2017. Acutely following focal cerebral ischemia disruption of the microvessel blood–brain barrier allows transit of plasma proteins into the neuropil as edema formation that coincides with loss of microvessel endothelial β1-integrins. We extend previous findings to show that interference with endothelial β1-integrin–matrix adhesion by the monoclonal IgM Ha2/5 increases the permeability of primary cerebral microvascular endothelial cell monolayers through reorganization of claudin-5, occludin, and zonula occludens-1 (ZO-1) from inter-endothelial borders. Interference with β1-integrin–matrix adhesion initiates F-actin conformational changes that coincide with claudin-5 redistribution. β1-integrin–matrix interference simultaneously increases phosphorylation of myosin light chain (MLC), while inhibition of MLC kinase (MLCK) and Rho kinase (ROCK) abolishes the Ha2/5-dependent increased endothelial permeability by 6 h after β1-integrin–matrix interference. These observations are supported by concordant observations in the cortex of a high-quality murine conditional β1-integrin deletion construct. Together they support the hypothesis that detachment of β1-integrins from abluminal matrix ligands increases vascular endothelial permeability through reorganization of tight junction (TJ) proteins via altered F-actin conformation, and indicate that the β1-integrin–MLC signaling pathway is engaged when β1-integrin detachment occurs. These findings provide a novel approach to the research and treatment of cerebral disorders where the breakdown of the blood–brain barrier accounts for their progression and complication.
- Access to Document (DOI)
A possible role of microglia-derived nitric oxide by lipopolysaccharide in activation of astroglial pentose-phosphate pathway via the Keap1/Nrf2 system.

2016.05

Research paper (scientific journal), Joint Work, Accepted
Dabigatran abrogates brain endothelial cell permeability in response to thrombin.

2015.06

Research paper (scientific journal), Joint Work, Accepted

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Papers, etc., Registered in KOARA 【 Display / hide 】

Beta1 integrin-pMLC endothelial permeability regulatory signaling as a novel therapeutic approach for neurological diseases

Izawa, Yoshikane

科学研究費補助金研究成果報告書 2020
Elucidation of novel beta 1 integrin-dependent mechanisms regulating vascular permeability

Izawa, Yoshikane

科学研究費補助金研究成果報告書 2018
Astrocytic neuroprotective mechanism against diabetic encephalopathy through metabolic stress response

Izawa, Yoshikane

科学研究費補助金研究成果報告書 2014

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

脳血管内皮透過性制御機構の解明による新規神経疾患治療法の確立

2021.04

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2024.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator
β1インテグリン-pMLC内皮透過性制御シグナルによる新規神経疾患治療法の確立

2019.04

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2021.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator
β1インテグリン/RhoK介在性・新規血管内皮透過性制御機構の解明

2017.04

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2019.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists (B), Principal investigator