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Investigating the Neuroprotective Effects of RIPC in Ischemic Stroke and Its Preventive Potential Through Combined Exercise Therapy

Research Project

Project/Area Number 22K17632
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionOita University (2024)
Kagoshima University (2022-2023)

Principal Investigator

Otsuka Shotaro  大分大学, 福祉健康科学部, 講師 (80849901)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2024: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords遠隔虚血コンディショニング / 予防運動 / 脳梗塞 / 神経保護効果 / 理学療法 / 白質病変 / RIPC / 内在性保護因子 / リハビリテーション医学 / リハビリテーション
Outline of Research at the Start

本研究は、脳梗塞に対する予防法を確立するために必要な基礎的なデータを得るために行うものである。習慣的な予防運動は、脳梗塞に対する予防効果を高めることが報告されているが、さらに遠隔虚血コンディショニング(Remote ischemic preconditioning;RIPC)を組み合わせることによって効果的な予防法を確立できる可能性がある。この可能性を追求するために、実験動物を使用した介入実験を行い、脳梗塞の縮小効果、神経麻痺の軽減効果を確認し、神経保護メカニズムを解析する。

Outline of Final Research Achievements

This study examined the neuroprotective effects of remote ischemic conditioning (RIPC) and exercise through animal experiments and human brain imaging. In animal models, RIPC applied during cerebral ischemia showed that longer reperfusion periods led to greater neuroprotection. A single RIPC session before stroke also reduced infarct volume, partly mediated by the myokine FNDC5/Irisin.
To assess neuroprotective effects of exercise in humans, we conducted a secondary analysis using MRI data. Higher physical activity levels and faster gait speed were associated with lower white matter hyperintensity (WMH) volumes, while higher IL-6 levels correlated with greater WMH. These findings suggest that RIPC and physical activity contribute to brain protection. Their combination may offer a promising non-invasive strategy for stroke prevention and neurological decline.

Academic Significance and Societal Importance of the Research Achievements

本研究では、体に軽い刺激を与える遠隔虚血コンディショニング(RIPC)や日常的な運動が、脳のダメージを防ぐ働きを持つことを、動物と人のデータから明らかにしました。特に、運動によって体内で作られる物質や活動量が、脳の老化や障害の進行を抑える可能性があることが分かりました。これにより、薬に頼らずに脳卒中や認知症を予防する新しい方法として、運動やRIPCの活用が期待されます。高齢者の健康寿命延伸にもつながる成果です。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (7 results)

All 2024 2023 2022

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Relationship between physical activity and cerebral white matter hyperintensity volumes in older adults with depressive symptoms and mild memory impairment: a cross-sectional study2024

    • Author(s)
      Otsuka Shotaro、Kikuchi Kiyoshi、Takeshita Yasufumi、Takada Seiya、Tani Akira、Sakakima Harutoshi、Maruyama Ikuro、Makizako Hyuma
    • Journal Title

      Frontiers in Aging Neuroscience

      Volume: 16

    • DOI

      10.3389/fnagi.2024.1337397

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of different remote ischemia perconditioning methods on cerebral infarct volume and neurological impairment in rats2023

    • Author(s)
      Otsuka Shotaro、Itashiki Yuki、Tani Akira、Matsuoka Teruki、Takada Seiya、Matsuzaki Ryoma、Nakanishi Kazuki、Norimatsu Kosuke、Tachibe Yuta、Kitazato Riho、Nojima Nao、Kakimoto Shogo、Kikuchi Kiyoshi、Maruyama Ikuro、Sakakima Harutoshi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 2158-2158

    • DOI

      10.1038/s41598-023-29475-2

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Stimulation of functional recovery via neurorepair mechanisms by the traditional Japanese Kampo medicine, Ninjin'yoeito, and physical exercise in a rat ischemic stroke model2023

    • Author(s)
      Tani Akira、Sakakima Harutoshi、Otsuka Shotaro、Mizuno Keita、Nakanishi Kazuki、Norimatsu Kosuke、Takada Seiya、Matsuoka Teruki、Matsuzaki Ryoma、Nakakogawa Tomomi、Maruyama Ikuro
    • Journal Title

      Journal of Ethnopharmacology

      Volume: 302 Pages: 115927-115927

    • DOI

      10.1016/j.jep.2022.115927

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of the Effects of Ninjin’yoeito on Physical Frailty in Mice2022

    • Author(s)
      Otsuka Shotaro、Fukumaru Keita、Tani Akira、Takada Seiya、Kikuchi Kiyoshi、Norimatsu Kosuke、Matsuzaki Ryoma、Matsuoka Teruki、Sakakima Harutoshi、Omiya Yuji、Mizuno Keita、Matsubara Yosuke、Maruyama Ikuro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 19 Pages: 11183-11183

    • DOI

      10.3390/ijms231911183

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Effects of remote ischemic pre-conditioning (RIPC) on brain damage and functional recovery after stroke in rats2023

    • Author(s)
      Teruki Matsuoka, Ryoma Matsuzaki, Akira Tani, Kosuke Norimatsu, Nao Nojima, Yuta Tachibe, Masaki Inadome, Shogo Kakimoto, Yuki Kato, Kazuki Nakanishi, Seiya Takada, Shotaro Otsuka, Harutoshi Sakakima
    • Organizer
      第46回神経科学学会
    • Related Report
      2023 Research-status Report
  • [Presentation] 異なる虚血再灌流時間が遠隔虚血パーコンディショニング(RIPerC)の神経保護効果に与える影響.2023

    • Author(s)
      大塚 章太郎、板敷 裕樹、松崎 凌真、松岡 輝樹、立部 勇汰、加藤 夕貴、柿元 翔吾、野島 菜央、稲留 真輝、谷 明.
    • Organizer
      第28回日本基礎理学療法学会学術大会
    • Related Report
      2023 Research-status Report
  • [Presentation] Preconditioning exercise in rats attenuates early brain injury resulting from subarachnoid hemorrhage by reducing oxidative stress, inflammation, and neuronal apoptosis.2022

    • Author(s)
      大塚 章太郎
    • Organizer
      NEURO2022
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research

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Published: 2022-04-19   Modified: 2026-01-16  

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