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Development of an animal model of post-stroke recrudescence and its imaging with diffusion tensor imaging

Research Project

Project/Area Number 20K09311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55060:Emergency medicine-related
Research InstitutionIwate Medical University

Principal Investigator

Akamatsu Yosuke  岩手医科大学, 医学部, 講師 (70835280)

Co-Investigator(Kenkyū-buntansha) 千田 光平  岩手医科大学, 医学部, 助教 (30611016)
藤原 俊朗  岩手医科大学, 薬学部, 講師 (60405842)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords既往脳卒中症状の再燃 / 感染症 / 拡散テンソル / 脳卒中後疲労 / 脳卒中後認知機能障害 / neuroinflammation / stroke / recrudescence / 脳卒中症状の再燃 / 炎症 / 脳卒中慢性期 / 白質障害
Outline of Research at the Start

脳卒中の既往を有する患者が、慢性期に感染を契機に既往の脳卒中症状の再燃を理由に救急受診することがあるが、これまで臨床経験に基づく報告があるのみで基礎研究は行われておらず病態は不明である。本研究では、マウス脳梗塞モデルの慢性期に全身性炎症を惹起して本病態を再現し、拡散テンソル画像を用いた病変の可視化と組織学的検討から神経障害の機序を解明し、本病態の予防法もしくは治療法の可能性を追求することである。

Outline of Final Research Achievements

In the present study, we aimed to develop animal model of post-stroke recrudescence (PSR) by inducing systemic inflammation at chronic stroke setting and detect white matter injury in the stroke model based on the value of fraction anisotropy calculated with diffusion tensor imaging at ultra-high field magnetic resonance imaging. In animal experiments, significant difference between the PSR group and non-PSR group in the value of fraction could not be detected, which might be related with unstable imaging condition. Besides that, by reviewing recent clinical and preclinical studies, correlation between upregulated immune responses to brain antigens and PSR, post-stroke fatigue, and dementia of which are associated with poor long-term stroke outcome were indicated. Therefore, the future of improving long-term stroke outcome could be bright with more accurate pre-clinical study focusing on the role of autoimmune response. Those contents were published as a review article.

Academic Significance and Societal Importance of the Research Achievements

既往脳卒中症状の再燃は、救急外来に脳卒中症状で来院する患者さんの10%を占めることが知られているが、病態は不明で治療法は確立していない。本研究では、動物モデルにおいて放射線画像上の大脳白質障害を指摘するに至らなかった。しかし、動物を用いた基礎研究や実際の患者さんの検体を用いた臨床研究から、脳卒中後の長期的な患者転帰に関わる脳卒中後疲労や認知症は脳細胞に対する免疫応答を介して起こることが示唆され、感染症を契機に起こることが多い既往脳卒中症状の再燃の病態に類似することは学術的意義がある。また、これらの病態の更なる解明が進むことで、脳卒中が後発する高齢者のADL改善が期待でき社会的な意義がある。

Report

(3 results)
  • 2023 Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2021 2020

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Post-stroke recrudescence-a possible connection to autoimmunity?2021

    • Author(s)
      Yosuke Akamatsu, Hersh J. Chaitin, Khalid A. Hanafy
    • Journal Title

      Reviews in the neurosciences

      Volume: 6 Issue: 2 Pages: 207-212

    • DOI

      10.1515/revneuro-2021-0062

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The role of TLR4 and HO-1 in neuroinflammation after subarachnoid hemorrhage2020

    • Author(s)
      Yosuke Akamatsu, Vicente A Pagan, Khalid A Hanafy
    • Journal Title

      Journal of Neuroscience Research

      Volume: 98 Issue: 3 Pages: 549-556

    • DOI

      10.1002/jnr.24515

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cell Death and Recovery in Traumatic Brain Injury2020

    • Author(s)
      Yosuke Akamatsu, Khalid A Hanafy
    • Journal Title

      Neurotherapeutics

      Volume: 17 Issue: 2 Pages: 446-456

    • DOI

      10.1007/s13311-020-00840-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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