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Study of functional recovery and neuroprotective mechanisms due to pre-and post-conditioning exercise in a stroke.

Research Project

Project/Area Number 17K01459
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Rehabilitation science/Welfare engineering
Research InstitutionKagoshima University

Principal Investigator

Harutoshi Sakakima  鹿児島大学, 医歯学域医学系, 教授 (10325780)

Co-Investigator(Kenkyū-buntansha) 樋口 逸郎  鹿児島大学, 医歯学域医学系, 教授 (80183573)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywordsリハビリテーション / 脳神経保護 / プレコンディショニング運動 / 運動療法 / 脳梗塞 / 脳神経科学 / 可塑性 / preconditioning exercise / 内因性保護因子 / 神経栄養因子 / 脳神経保護効果 / アポトーシス / 14-3-3γ / 抗アポトーシス効果 / 予防運動 / 神経保護 / アポトーシス抑制
Outline of Final Research Achievements

We firstly investigated the anti-apoptosis mechanism of enhanced 14-3-3γ mediated by preconditioning exercise-induced brain ischemic tolerance after stroke. Secondly, we examined the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats. Preconditioning exercise prior to ischemia induces neuron- and astrocyte-mediated brain ischemic tolerance through increased expression of HIF-1α and 14-3-3γ, which are intrinsic protective factors; the upregulated 14-3-3γ induced by preconditioning exercise reduces ischemic neuronal cell death through the 14-3-3γ/p-β-catenin Ser37/Bax/caspase-3 anti-apoptotic pathway. Furthermore, three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke.

Academic Significance and Societal Importance of the Research Achievements

日々の運動習慣は生活習慣病の予防に重要だけでなく脳卒中発症の予防効果が期待できることが知られている。近年、規則的な運動を行うことによって、たとえ脳梗塞が発症したとしても、脳梗塞巣の縮小効果や機能回復促進効果が期待できることが報告されている。本研究成果は、日々の規則的な運動習慣による脳神経保護効果の脳内メカニズムの解明を目指すものであり学術的意義が高い。さらに、予防リハビリテーション分野へ臨床応用するために、神経保護効果を期待できる適切な運動条件を明らかにする臨床へのトランスレーションを目的にした研究成果であり社会的意義は大きい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (8 results) (of which Invited: 1 results)

  • [Journal Article] Endogenous neuroprotective potential due to preconditioning exercise in stroke2019

    • Author(s)
      Sakakima H.
    • Journal Title

      Physical Therapy Research

      Volume: 22 Issue: 2 Pages: 45-52

    • DOI

      10.1298/ptr.R0006

    • NAID

      130007769930

    • ISSN
      2189-8448
    • Year and Date
      2019-12-20
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroprotective effects of different frequency preconditioning exercise on neuronal apoptosis after focal brain ischemia in rats.2019

    • Author(s)
      Terashi T, Otsuka S, Takada S, Nakanishi K, Ueda K, Sumizono M, Kikuchi K, Sakakima H.
    • Journal Title

      Neurol Res.

      Volume: 41 Issue: 6 Pages: 510-518

    • DOI

      10.1080/01616412.2019.1580458

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Preconditioning exercise reduces brain damage and neuronal apoptosis through enhanced endogenous 14-3-3γ after focal brain ischemia in rats.2019

    • Author(s)
      Otsuka S, Sakakima H, Terashi T, Takada S, Nakanishi K, Kikuchi K.
    • Journal Title

      Brain Struct Funct

      Volume: 224(2) Issue: 2 Pages: 727-738

    • DOI

      10.1007/s00429-018-1800-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Preconditioning exercise reduces ischemia reperfusion-induced focal cerebral infarct volume and neuronal apoptosis through enhanced endogenous 14-3-3gamma after focal brain ischemia in rats.2019

    • Author(s)
      Shotaro Otuka, Seiya Takada, Kazuki Nakanishi, Harutoshi Sakakima.
    • Organizer
      日本神経科学学会2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳虚血中の遠隔虚血性コンディショニングが脳保護効果に及ぼす影響2019

    • Author(s)
      板敷裕喜、大塚章太郎、谷明、高田聖也、中西和毅、則松貢輔、榊間春利.
    • Organizer
      第18回コ・メディカル形態機能学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] クモ膜下出血後の早期脳損傷に対する予防運動の効果2019

    • Author(s)
      大塚章太郎、高田聖也、中西和毅、則松貢輔、板敷裕喜、谷明、菊池清志、丸山征郎、榊間春利
    • Organizer
      第18回コ・メディカル形態機能学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neuroprotective effect of different frequency preconditioning exercise on down-regulation of Bax/Bcl-2 confers apoptosis after cerebral infarction in rats.2018

    • Author(s)
      Takuto Terashi, Shotaro Otsuka, Seiya Takada, Kazuki Nakanishi, Koki Ueda, Megumi Sumizono, Harutoshi Sakakima.
    • Organizer
      日本神経科学学会2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 脳梗塞発症前運動による脳虚血耐性の獲得と脳梗塞後の14-3-3γ発現を介したアポトーシス抑制2018

    • Author(s)
      大塚章太郎、高田聖也、中西和毅、板敷裕喜、則松孝輔、谷明、榊間春利
    • Organizer
      第23回日本基礎理学療法学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 運動と脳神経保護2018

    • Author(s)
      榊間春利
    • Organizer
      第3回基礎理学療法学術大会 夏の学校
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Neuroprotective effect of different frequency preconditioning exercise on down-regulation of Bax/Bcl-2 confers apoptosis after cerebral infarction in rats2018

    • Author(s)
      Takuto Terashi, Shotaro Otsuka, Seiya Takada, Kazuki Nakanishi, Koki Ueda, Megumi Sumizono, Harutoshi Sakakima
    • Organizer
      第41回日本神経科学学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 定期的なトレッドミル運動によるラット脳梗塞後の神経保護効果とその作用機序について2017

    • Author(s)
      大塚章太郎、寺師拓斗、上田晃希、中西和毅、高田聖也、角園恵、榊間春利;
    • Organizer
      第16回コメディカル形態機能学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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