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Adaptation of the neuroprotective mechanism by conditioning after cerebral ischemia and its application to stroke rehabilitation

Research Project

Project/Area Number 20H04039
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59010:Rehabilitation science-related
Research InstitutionKagoshima University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 丸山 征郎  鹿児島大学, 医歯学総合研究科, 客員研究員 (20082282)
前島 洋  北海道大学, 保健科学研究院, 教授 (60314746)
菊池 清志  久留米大学, 医学部, 准教授 (60404539)
大塚 章太郎  鹿児島大学, 医歯学総合研究科, 特任助教 (80849901)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2020: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords運動 / 遠隔虚血コンディショニング / 脳神経保護 / リハビリテーション / 機能回復 / 神経炎症 / 漢方薬 / 脳梗塞 / 予防運動 / 神経可塑性 / 脳卒中リハビリテーション / コンディショニング運動 / プレコンディショニング / 予防 / 認知症 / 脳梗塞モデル / コンディショニング / 有酸素運動 / 活動量 / 高齢者
Outline of Research at the Start

脳虚血による神経障害は多数の因子が相互に作用し進展するため、治療対象として単独のタンパクやシグナル伝達系の調節を行う事ではその効果に限界があり、複数の因子を一度に調節する治療が有効であると考えられる。これが可能な方法として遠隔虚血コンディショニング(Remote ischemic conditioning: RIC)による脳虚血耐性の獲得や発症前の有酸素運動(Pre-conditioning Exercise:PE)による脳神経保護効果がある。本研究では、研究期間全体を通して、RICやPEの脳神経保護メカニズムの解明と脳卒中患者のリハビリテーションに応用すべく臨床疫学調査を行う。

Outline of Final Research Achievements

In this research project, we investigated the mechanisms of neuroprotection by pre-conditioning exercise (PE) and remote ischemic conditioning (RIC). Preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. The duration of reperfusion may affect the brain protective effect. Notably, RIPerC with a reperfusion time of approximately 10 min exerts its neuroprotective effects via an anti-apoptotic mechanism. Ninjin’yoeito (NYT) in combination with exercise provides neuroprotective effects and improves sensorimotor function by stimulating NGF/TrkA and BDNF/TrkB, and by activating the Akt pathway in ischemic stroke of rats. Low-intensity motor balance and coordination exercise prevented age-related cognitive decline in the early stage of AD progression, possibly through the suppression of hippocampal Aβ deposition, neuronal loss, oxidative stress, and neuroinflammation, including reduced M1 and A1 phenotypes microglia and astrocytes.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞発症前・後のPE、RIC、運動療法による脳神経保護メカニズムや認知・機能回復促進効果、リハビリテ-ション処方に重要である効果的な負荷量、頻度、時間などに関しては十分解明されていない。また、運動習慣の有無による脳保護効果、認知機能に及ぼす影響、運動機能改善効果、RICとPEの併用効果、薬剤と運動療法の併用効果などに関しても十分解明されていない。従って、本研究成果の学術的意義や社会的意義は、運動や遠隔虚血コンディショニングによる神経保護メカニズムを解明し、脳卒中リハビリテーションや認知症に対する予防リハビリテーションの科学的根拠を確立したことである。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (20 results)

All 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (12 results) (of which Invited: 2 results)

  • [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
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of early exercise intervention and exercise cessation on neuronal loss and neuroinflammation in a senescence-accelerated mouse prone 82023

    • Author(s)
      Nakanishi Kazuki、Norimatsu Kosuke、Tani Akira、Matsuoka Teruki、Matsuzaki Ryoma、Kakimoto Shogo、Nojima Nao、Tachibe Yuta、Kato Yuki、Inadome Masaki、Kitazato Riho、Otsuka Shotaro、Takada Seiya、Sumizono Megumi、Sakakima Harutoshi
    • Journal Title

      Neuroscience Letters

      Volume: 808 Pages: 137297-137297

    • DOI

      10.1016/j.neulet.2023.137297

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of low-intensity exercise on spontaneously developed knee osteoarthritis in male senescence-accelerated mouse prone 82023

    • Author(s)
      Norimatsu Kosuke、Nakanishi Kazuki、Ijuin Toshiro、Otsuka Shotaro、Takada Seiya、Tani Akira、Matsuzaki Ryoma、Matsuoka Teruki、Sakakima Harutoshi
    • Journal Title

      Arthritis Research & Therapy

      Volume: 25 Issue: 1 Pages: 168-168

    • DOI

      10.1186/s13075-023-03162-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats2021

    • Author(s)
      Otsuka Shotaro、Sakakima Harutoshi、Tani Akira、Nakanishi Kazuki、Takada Seiya、Norimatsu Kosuke、Maejima Hiroshi、Maruyama Ikuro
    • Journal Title

      Brain Structure and Function

      Volume: 226 Issue: 7 Pages: 2169-2180

    • DOI

      10.1007/s00429-021-02317-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis2021

    • Author(s)
      Otsuka Shotaro、Setoyama Kentaro、Takada Seiya、Nakanishi Kazuki、Terashi Takuto、Norimatsu Kosuke、Tani Akira、Sakakima Harutoshi、Maruyama Ikuro、Tancharoen Salunya、Tanaka Eiichiro、Kikuchi Kiyoshi
    • Journal Title

      Molecular Neurobiology

      Volume: 58 Issue: 11 Pages: 5602-5617

    • DOI

      10.1007/s12035-021-02506-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Aβ deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer's disease2021

    • Author(s)
      Nakanishi K, Sakakima H, Norimatsu K, Otsuka S, Takada S, Tani A, Kikuchi K.
    • Journal Title

      Exp Neurol.

      Volume: 337 Pages: 113590-113590

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diurnal Profiles of Locomotive and Household Activities Using an Accelerometer in Community-Dwelling Older Adults with Musculoskeletal Disorders: A Cross-Sectional Survey2020

    • Author(s)
      Sakakima H, Takada S, Norimatsu K, Otsuka S, Nakanishi K, Tani A.
    • Journal Title

      Int J Environ Res Public Health

      Volume: 17 Issue: 15 Pages: 5537-5537

    • DOI

      10.3390/ijerph17155337

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ラット脳梗塞後の運動療法と人参養栄湯の併用治療は感覚運動機能の回復を促進する2023

    • Author(s)
      谷明、中西和毅、松岡 輝樹、松崎凌真、野島菜央、立部勇汰、柿元翔吾、稲留真輝、加藤夕貴、榊間春利.
    • Organizer
      第28回基礎理学療法学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 早期運動介入と運動中止がアルツハイマー病モデル動物の認知機能低下や海馬に及ぼす影響2023

    • Author(s)
      中西和毅、則松貢輔、谷明、松﨑凌真、松岡輝樹、加藤夕貴、柿元翔吾、立部勇汰、野島菜央、榊間春利
    • Organizer
      第28回基礎理学療法学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 神経疾患に対する理学療法の効果検証2023

    • Author(s)
      榊間春利
    • Organizer
      第28回基礎理学療法学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 脳保護を考慮した運動療法2023

    • Author(s)
      榊間春利
    • Organizer
      第45回日本高血圧学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 老化促進マウス(SAMP8)の膝関節軟骨の加齢変化と低強度トレッドミル運動の影響2023

    • Author(s)
      榊間春利、則松貢輔、中西和毅、大塚章太郎、高田聖也、松崎凌真、谷明、中小川智美、松岡輝樹、稲留真輝、加藤夕貴、柿元翔吾、野島菜央、立部勇太.
    • Organizer
      第128回日本解剖学会総会・全国学術集会
    • Related Report
      2023 Annual Research 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, 松岡輝樹, 松崎凌真, 中小川智美, 谷明, 則松貢輔, 高田聖也, 中西和毅, 丸山征郎, 榊間春利 , 菊池清志
    • Organizer
      第45回日本神経科学大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Stimulation of functional recovery via the mechanisms of neurorepair by Japanese herbal medicine, Ninjinyoeito, and physical exercise in a rat ischemic stroke model.2021

    • Author(s)
      Tani A, Nakanishi K, Otsuka S, Norimatsu K, Takada S, Matsuoka T, Sakakima H
    • Organizer
      第44回日本神経科学学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Effects of low-intensity balance and coordination exercise on cognitive function, hippocampal Aβ deposition, neuronal loss, neuroinflammation, and oxidative stress in SAMP8.2021

    • Author(s)
      Nakanishi K, Norimatsu K, Otsuka S, Takada S, Tani A, Sakakima H.
    • Organizer
      第44回日本神経科学学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Effects of aging and balance exercise on the knee joint of the senescence accelerated mouse (SAMP8).2021

    • Author(s)
      Norimatsu K, Nakanishi K, Tani A, Fukumaru K, Otsuka S, Takada S, Sakakima H.
    • Organizer
      第126回日本解剖学会総会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Midkine gene deficiency attenuates traumatic brain injury through regulation of microglia and macrophage polarization.2020

    • Author(s)
      Seiya Takada, Takahiro Matsuyama, Shotaro Otsuka1, Kazuki Nakanishi, Kosuke Norimatsu, Yuki Itashiki, Akira Tani, Kiyoshi Kikuchi, Harutoshi Sakakima.
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of detraining on neuroprotective effects due to preconditioning exercise-induced brain tolerance after ischemic stroke of rat.2020

    • Author(s)
      Shotaro Otsuka, Akira Tani, Yuki Itashiki, Kosuke Norimatu, Seiya Takada, Kazuki Nakanishi, Maruyama Ikuro, Harutoshi Sakakima.
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] The neuroprotective effects of remote ischemic per-conditioning on focal brain ischemia of rats.2020

    • Author(s)
      Akira Tani, Yuki Itashiki, Shotaro Ohtsuka, Seiya Tankada, Kazuki Nakanishi, Kosuke Norimatsu, Harutoshi Sakakima.
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Annual Research Report

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

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