• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of exercise therapy combined with pharmacological treatment of synaptic transmission for stroke rehabilitation

Research Project

Project/Area Number 17H02117
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Rehabilitation science/Welfare engineering
Research InstitutionHokkaido University

Principal Investigator

Maejima Hiroshi  北海道大学, 保健科学研究院, 教授 (60314746)

Co-Investigator(Kenkyū-buntansha) 真先 敏弘  帝京科学大学, 医学教育センター, 教授 (00585028)
榊間 春利  鹿児島大学, 医歯学域医学系, 教授 (10325780)
齊藤 展士  北海道大学, 保健科学研究院, 助教 (60301917)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsリハビリテーション / 脳卒中 / 運動 / GABA受容体 / コンディショニング / 神経栄養因子 / シナプス
Outline of Final Research Achievements

This study elucidated the effects of daily combined therapy of treadmill exercise (11m/min) and administration of GABAA receptor inhibitor (bicuculline, 0.25mg/kg) for 2 weeks on motor recovery and neurological modification in the motor cortex. Middle cerebral artery occlusion (MCAO) surgery impaired motor function of the paralyzed limbs and decreased the protein expression of brain derived neurotrophic factor (BDNF) in the ipsilateral motor cortex. Neither bicuculline administration nor treadmill exercise recovered motor function, whereas treadmill exercise combined with bicuculline administration improved motor function, accompanying the increase of protein BDNF expression in the ipsilateral motor cortex. This study showed the combined therapy with exercise and the inhibition of GABAergic synapses facilitates motor recovery accompanied by the increase of BDNF expression in the ipsilateral motor cortex in the model rats of ischemic stroke.

Academic Significance and Societal Importance of the Research Achievements

脳卒中後の機能回復を目的とするリハビリテーションにおいて、運動療法は中枢神経系の可塑的変化を誘導し機能回復を促進する中心的な治療介入であるが、その治療効果を最大限有効にするため、運動療法に対する事前の神経賦活化コンディショニングが期待される。本研究は、GABA受容体阻害下における運動は相乗的に脳卒中後の運動機能回復を促進し、損傷脳におけるBDNF発現を増強することを明らかとした。従って、抑制性シナプス伝達の薬理的阻害は、脳卒中リハビリテーションにおける運動療法効果を増強するための有益な中枢性コンディショニングとなり得ることを示す基礎研究として本研究は学術的意義を有している。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (10 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] Exercise plus pharmacological neuromodulation of synaptic inhibition enhance motor function recovery after ischemic stroke2020

    • Author(s)
      Inoue T., Okamura M., Kitahara M., Takamatsu Y., Sakakima H., Maejima H.
    • Journal Title

      Neuroscience

      Volume: 430 Pages: 12-24

    • DOI

      10.1016/j.neuroscience.2020.01.012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic exercise accompanied by neuronal modulation to enhance neurotrophic factors in the brain with central nervous system disorders2019

    • Author(s)
      Maejima H., Inoue T., Takamatsu Y.
    • Journal Title

      Physical Therapy Research

      Volume: 22 Issue: 1 Pages: 38-43

    • DOI

      10.1298/ptr.R0004

    • NAID

      130007665699

    • ISSN
      2189-8448
    • Year and Date
      2019-06-20
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exercise and low-level GABAA receptor inhibition modulate locomotor activity and the expression of BDNF accompanied by changes in epigenetic regulation in the hippocampus2018

    • Author(s)
      Maejima H., Ninuma S., Okuda A., Inoue T., Hayashi M.
    • Journal Title

      Neuroscience Letters

      Volume: 685 Pages: 18-23

    • DOI

      10.1016/j.neulet.2018.07.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Combination of exercise and pharmacological neuromodulation targeting GABAA receptors promotes motor recovery and BDNF protein expression in the M1 after focal brain ischemia in rats2019

    • Author(s)
      Inoue T., Kitahara M., Okamura M., Maejima H.
    • Organizer
      The Society for Neuroscience 48th Annual Meeting (Neuroscience 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Voluntary exercise combined with repetitive inhibition of GABAergic synapses modulates the expression of BDNF in the motor cortex.2019

    • Author(s)
      Maejima H., Hayashi M., Inoue T., Kitahara M.
    • Organizer
      The Society for Neuroscience 48th Annual Meeting (Neuroscience 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Treadmill exercise beneficially contributes to gene expressions relating to synaptic and axonal plasticity in the motor cortex after ischemic stroke in rats.2019

    • Author(s)
      Inoue T. Okamura M., Kitahara M., Takamatsu Y., Maejima H.
    • Organizer
      The 1st International Sport Neuroscience Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Exercise combined with low-level GABAA receptor inhibition modulates the expression of neurotrophins in the cerebellum.2019

    • Author(s)
      Maejima H., Ikuta G., Takahashi K.
    • Organizer
      The 1st International Sport Neuroscience Conference
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effects of low-intensity exercise on the gene expressions relating to synaptic plasticity in the hippocampus following ischemic stroke in rats.2019

    • Author(s)
      Okamura M., Inoue T., Kako Y., Takamatsu H., Maejma H.
    • Organizer
      The 42st Annual Meeting of the Japan Neurosciece Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The interactive effects of GABA receptor antagonist and exercise on the recovery of motor function and BDNF expression in the ipsilesional M1 after ischemic stroke in rats.2019

    • Author(s)
      Inoue T., Takamatsu Y., Maejima H.
    • Organizer
      The 42st Annual Meeting of the Japan Neurosciece Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Site-specific modulation of BDNF expression in the brain following chronic GABAA receptor inhibition.2018

    • Author(s)
      Maejima H., Kitahara M., Hayashi M., Inoue T., Li X.
    • Organizer
      FENS Forum 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Low-level inhibition of GABAA receptor and motor exercise modulate BDNF expression in the motor related cortex.2018

    • Author(s)
      Inoue T., Ninuma N., Hayashi M., Okuda A., Asaka T., Maejima H.
    • Organizer
      The 41st Annual Meeting of the Japan Neurosciece Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エピジェネティクス制御を伴う脳由由来神経栄養因子の運動依存的発現修飾2018

    • Author(s)
      前島 洋
    • Organizer
      日本基礎理学療法学会 夏の学校
    • Related Report
      2018 Annual Research Report
  • [Presentation] GABA受容体阻害下の運動療法が脳卒中後の機能回復に与える影響2018

    • Author(s)
      井上貴博, 林 正隆, 李 想, 北原美佳, 前島 洋
    • Organizer
      第23回日本基礎理学療法学会学術大会
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi