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Mechanism of endothelial dysfunction in the acute brain ischemia and development of therapeutic intervention.

Research Project

Project/Area Number 21591080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionOsaka University

Principal Investigator

YAGITA Yoshiki  大阪大学, 医学系・研究科, 助教 (20403066)

Co-Investigator(Kenkyū-buntansha) KITAGAWA Kazuo  大阪大学, 医学系・研究科, 准教授 (70301257)
Research Collaborator SAKODA Saburo  刀根山病院, 院長
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脳虚血 / 血管内皮 / 微小循環障害 / Rho-kinase / 一酸化窒素合成酵素 / 脳小血管病
Research Abstract

Endothelial nitric oxide synthase(eNOS) is one of key molecules to maintain endothelial function. Although eNOS expression was increased in the brain small vessels after cerebral ischemia, phosphorylation level of Ser1177 of eNOS molecule was significantly reduced, indicating eNOS dysfunction. Rho-kinase inhibitor can ameliorate ischemic injury via increasing eNOS phosphorylation. Hypertension also decreased eNOS phosphorylation in the brain small vessels and deteriorated ischemic injury, and anti-hypertensive therapy could preserve eNOS phosphorylation. Additionally, phosphodiesterase3 could preserve eNOS phosphoryaltion and function and ameliorated cerebral ischemic injury. These results may contribute to develop new therapy for acute brain ischemia and brain small vessel disease.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (16 results)

All 2011 2010 2009 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (4 results) Remarks (2 results)

  • [Journal Article] Cilostazol, not aspirin, reduces ischemic brain injury via endothelial protection in spontaneously hypertensive rats2011

    • Author(s)
      Oyama N, Yagita Y, Kawamura M, Sugiyama Y, Terasaki Y, Omura-Matsuoka E, Sasaki T, Kitagawa K.
    • Journal Title

      Stroke

      Volume: 42(9) Pages: 2571-2577

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cilostazol, not aspirin, reduces ischemic brain injury via endothelial protection in spontaneously hypertensive rats2011

    • Author(s)
      Oyama N, Yagita Y, et al
    • Journal Title

      Stroke

      Volume: 89 Issue: 9 Pages: 2571-2577

    • DOI

      10.1161/strokeaha.110.609834

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 局所脳虚血モデルにおける内皮型一酸化窒素合成酵素の発現動態2011

    • Author(s)
      八木田佳樹, 他
    • Journal Title

      脳循環代謝

      Volume: 22 Pages: 29-34

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Hypertension impairs leptomeningeal collateral growth after common carotid artery occlusion : restoration by antihypertensive treatment.2011

    • Author(s)
      Omura-Matsuoka E, Yagita Y, et al.
    • Journal Title

      J Neurosci Res.

      Volume: 89 Pages: 108-116

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats2010

    • Author(s)
      Oyama N, Yagita Y, Sasaki T, Omura-Matsuoka E, Terasaki Y, Sugiyama Y, Sakoda S, Kitagawa K.
    • Journal Title

      J Neurosci Res

      Volume: 88(13) Pages: 2889-2898

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] An angiotensin II type 1 receptor blocker can preserve endothelial function and attenuate brain ischemic damage in spontaneously hypertensive rats.2010

    • Author(s)
      Oyama N, Yagita Y, et al.
    • Journal Title

      J Neurosci Res.

      Volume: 88 Pages: 2889-2898

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of NR2A receptors induces ischemic tolerance through CREB signaling2010

    • Author(s)
      Terasaki Y, Sasaki T, Yagita Y, et al.
    • Journal Title

      J Cereb Blood Flow Metab. (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-cadherin mediates interaction between precursor cells in the subventricular zone and regulates further differentiation2009

    • Author(s)
      Yagita Y, et al.
    • Journal Title

      J Neurosci Res. 87

      Pages: 3331-3342

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postischemic administration of angiotensin II type 1 receptor blocker reduces cerebral infarction size in hypertensive rats2009

    • Author(s)
      Omura-Matsuoka E, Yagita Y, et al.
    • Journal Title

      Hypertens Res. 32

      Pages: 548-553

    • NAID

      10025163958

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Granulocyte Colony-Stimulating Factor Enhances Arteriogenesis and Ameliorates Cerebral Damage in a Mouse Model of Ischemic Stroke.

    • Author(s)
      Sugiyama Y, Yagita Y, et al.
    • Journal Title

      Stroke.

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Cilostazol but Not Aspirin can Maintain Cerebrovascular Function in Spontaneously Hypertensive Rats2011

    • Author(s)
      Naoki Oyama, Yoshiki Yagita, Tsutomu Sasaki, Emi Omura-Matsuoka, Yasukazu Terasaki, Yukio Sugiyama, Miki Kawamura, Kazuo Kitagawa
    • Organizer
      Spontaneously Hypertensive Rats
    • Place of Presentation
      Los Angels, USA
    • Related Report
      2011 Final Research Report
  • [Presentation] Rho-kinase inhibitor can enhance endothelial nitric oxide synthase phosphorylation and suppress the infarct expansion after focal cerebral ischemia2010

    • Author(s)
      八木田佳樹, 他
    • Organizer
      日本神経科学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-09-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] Phosphorylation of endothelial nitric oxide synthase is increased by Rho-kinase inhibition in the brain2009

    • Author(s)
      Yagita Y, et al.
    • Organizer
      Brain 09 (国際脳循環代謝学会)
    • Place of Presentation
      シカゴ (アメリカ)
    • Year and Date
      2009-06-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Downregulation of endothelial nitric oxide synthase phosphorylation contributes to infarct expansion after focal cerebral ischemia2009

    • Author(s)
      Yoshiki Yagita, Tsutomu Sasaki, Naoki Oyama, Yukio Sugiyama, Yasukazu Terasaki, Emi Omura-Matsuoka, Kazuo Kitagawa
    • Organizer
      International Stroke Conference
    • Place of Presentation
      Los Angels, USA
    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.osaka-njm.net/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.osaka-njm.net/labo

    • Related Report
      2011 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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