Izawa, Yoshikane

写真a

Affiliation

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

Position

Assistant Professor/Senior Assistant Professor

Career 【 Display / hide

  • 2003.05
    -
    2005.04

    慶應義塾大学医学部研修医(内科)

  • 2007.04
    -
    2009.09

    慶應義塾大学医学部神経内科

  • 2009.10
    -
    2011.10

    慶應義塾大学脳血管障害予防医学寄附講座

  • 2011.11
    -
    2014.10

    University of Washington, School of Medicine, Division of Hematology

  • 2014.11
    -
    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

 

Research Keywords 【 Display / hide

  • Neurovsacular unit

  • 脳血管障害 Cerebrovascular disease

  • 血液脳関門 Blood brain barrier

 

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

     View Summary

    © 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.

  • 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

     View Summary

    © 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.

  • 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

     View Summary

    © 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.

  • 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

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

  • 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, 伊澤 良兼, 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, 伊澤 良兼, Grant-in-Aid for Young Scientists (B), Principal Investigator

 

Courses Taught 【 Display / hide

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2021

  • LECTURE SERIES, INTERNAL MEDICINE

    2021

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2020

  • LECTURE SERIES, INTERNAL MEDICINE

    2020

  • LECTURE SERIES, INTERNAL MEDICINE

    2019

 

Memberships in Academic Societies 【 Display / hide

  • 日本脳循環代謝学会, 

    2008.10
    -
    Present
  • 日本脳卒中学会, 

    2008.01
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    Present
  • 日本神経学会, 

    2007.04
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    Present
  • 日本内科学会, 

    2003.07
    -
    Present

Committee Experiences 【 Display / hide

  • 2016.11
    -
    Present

    日本脳循環代謝学会評議員