The role of exercise on the oligodendrogenesis and recovery of motor functions in focal stroke model in rats

• Project/Area Number: 17K01482
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Rehabilitation science/Welfare engineering
• Research Institution: Tokoha University
• Principal Investigator: KUMADA Tatsuro 常葉大学, 保健医療学部, 教授 (00402339)
• Co-Investigator(Kenkyū-buntansha): 梅村 和夫 浜松医科大学, 医学部, 教授 (40232912) ; 吉川 輝 昭和大学, 医学部, 助教 (90737355)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: stroke / recovery / exercise / 脳梗塞 / リハビリテーション / オリゴデンドロサイト / 運動処方 / 髄鞘 / 脳梗塞モデル動物 / 運動療法

Outline of Final Research Achievements

Exercise therapy significantly contributes to functional recovery after cerebral infarction. However, its neurological mechanism is not well understood. We developed a focal cerebral infarction model in rats to investigate the effect of various exercise training on the recovery of motor function and the reconstruction/reorganization of the nervous system. Here, we focused on the generation of oligodendrocyte progenitor cells as well as neurons from neural stem cells. Beam-walikng test revealed that motor recovery was different in time-dependent manner, showing a biphasic recovery process after post-operation. There were apparent differences in the effect of various exercises in the later stages. In addition, BrdU labeling experiments revealed that low-intensity exercises which had most effective tended to increase the number of neurons and oligodendrocyte progenitor cells during this period.

Academic Significance and Societal Importance of the Research Achievements

近年、中枢神経系の損傷後に内在性の幹細胞が新たに増殖分化する事が機能の回復に関与する事が見出され、潜在的な可塑性を引き出す重要性が示唆されている。このような神経系の再構築とリハビリテーションの関わりに関する知見は未だ少ない。我々は局在性脳梗塞モデル動物に対する様々な運動処方が運動機能の回復とオリゴデンドロサイトの前駆細胞を含む細胞新生に対する影響について調べた。身体機能と脳内での変化に基づく運動処方の在り方を考える上でのエビデンスを示唆できたと考えている。

Research Products

• [Journal Article] Different exercises can modulate the differentiation/maturation of neural stem/progenitor cells after photochemically induced focal cerebral infarction (2020)
  • Author(s): Morishita Saho、Hokamura Kazuya、Yoshikawa Akira、Agata Nobuhide、Tsutsui Yoshihiro、Umemura Kazuo、Kumada Tatsuro
  • Journal Title: Brain and Behavior Volume: 10 Issue: 3 Pages: 1535-1535
  • DOI: 10.1002/brb3.1535
  • Peer Reviewed / Open Access
• [Journal Article] G-protein-coupled receptor 40 agonist GW9508 potentiates glucose-stimulated insulin secretion through activation of protein kinase Cα and ε in INS-1 cells (2019)
  • Author(s): Hashimoto Takuya、Mogami Hideo、Tsuriya Daisuke、Morita Hiroshi、Sasaki Shigekazu、Kumada Tatsuro、Suzuki Yuko、Urano Tetsumei、Oki Yutaka、Suda Takafumi
  • Journal Title: PLOS ONE Volume: 14 Issue: 9 Pages: e0222179-e0222179
  • DOI: 10.1371/journal.pone.0222179
  • Peer Reviewed / Open Access
• [Journal Article] A Potential New Risk Factor for Stroke: Streptococcus Mutans With Collagen-Binding Protein. (2018)
  • Author(s): Inenaga C, Hokamura K, Nakano K, Nomura R, Naka S, Ohashi T, Ooshima T, Kuriyama N, Hamasaki T, Wada K, Umemura K, Tanaka T
  • Journal Title: World Neurosurgery Volume: 113 Pages: 77-81
  • DOI: 10.1016/j.wneu.2018.01.158
  • Peer Reviewed / Open Access
• [Journal Article] Increase in blood-brain barrier permeability does not directly induce neuronal death but may accelerate ischemic neuronal damage (2018)
  • Author(s): Chiemi Ohmori, Yusuke Sakai, Yasuki Matano, Yasuhiro Suzuki, Kazuo Umemura and Nobuo Nagai
  • Journal Title: Experimental Animals Volume: 67 Issue: 4 Pages: 479-486
  • DOI: 10.1538/expanim.18-0038
  • NAID: 40021698493
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study. Frontiers in Psychology (2018)
  • Author(s): Watanabe K, Masaoka Y, Kawamura M, Yoshida M, Koiwa N, Yoshikawa A, Kubota S, Ida M, Ono K, Izumizaki M
  • Journal Title: Frontiers in Psychology Volume: 9 Pages: 687-687
  • DOI: 10.3389/fpsyg.2018.00687
  • Peer Reviewed / Open Access
• [Journal Article] Comparative Study of Effects of Vonoprazan and Esomeprazole on Antiplatelet Function of Clopidogrel or Prasugrel in Relation to CYP2C19 Genotype. (2018)
  • Author(s): Kagami T, Yamade M, Suzuki T, Uotani T, Hamaya Y, Iwaizumi M, Osawa S, Sugimoto K, Umemura K, Miyajima H, Furuta T.
  • Journal Title: Clin Pharmacol Ther. Volume: 103 Issue: 5 Pages: 906-913
  • DOI: 10.1002/cpt.863
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects. (2017)
  • Author(s): Umemura K, Ikeda Y, Matsushima N, and Kondo K
  • Journal Title: Clin Pharmacol Drug Dev Volume: 6 Issue: 4 Pages: 398-407
  • DOI: 10.1002/cpdd.308
  • Peer Reviewed
• [Journal Article] Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel. (2017)
  • Author(s): Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani T, Sahara S, Ichikawa H, Kagami T, Iwaizumi M, Hamaya Y, Osawa S, Sugimoto K, Umemura K.
  • Journal Title: J Thromb Thrombolysis. Volume: 43 Issue: 3 Pages: 333-342
  • DOI: 10.1007/s11239-016-1460-2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Mutation in a highly conserved glycine residue in strand 5B of plasminogen activator inhibitor 1 causes polymerization. (2017)
  • Author(s): Iwaki T, Nagahashi K, Takano K, Suzuki-Inoue K, Kanayama N, Umemura K, Urano T.
  • Journal Title: Thrombosis and Haemostasis Volume: 117(5) Issue: 05 Pages: 860-869
  • DOI: 10.1160/th16-07-0572
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Detection of motor defects in hindlimbs during locomotion in rats with focal cerebral infarction by 3D kinematical analysis (2020)
  • Author(s): 熊田竜郎, 吉川輝, 森下紗帆, 外村和也, 泉崎雅彦, 梅村和夫
  • Organizer: 第97回日本生理学会
• [Presentation] Three-dimensional kinematical gait analysis of hindlimbs in rats with focal cerebral infarction. (2019)
  • Author(s): Kumada, T., Yoshikawa, A., Morishita, S., Hokamura, K., Izumizaki, M., Umemura, K
  • Organizer: 9th FAOPS (Federation of the Asian and Oceanian Physiological Societies) Congress
  • Int'l Joint Research
• [Presentation] Three-dimensional kinematic evaluation of motor dysfunction in a rat model of photochemically induced focal stroke. (2018)
  • Author(s): Yoshikawa, A., Morishita, S., Hokamura, K., Umemura, K., Izumizaki, M., and Kumada, T.
  • Organizer: The 42st Annual Meeting, Society for Neuroscience,
  • Int'l Joint Research
• [Presentation] Effect of different exercises on the differentiation of neural stem cells and motor recovery in rats with motor cortex infarction. (2018)
  • Author(s): 森下紗帆, 外村和也, 吉川輝, 縣信秀, 梅村和夫, 筒井祥博, 熊田竜郎
  • Organizer: 第95回日本生理学会大会
• [Presentation] Effects of various exercises on motor recovery through gating and neuro/gliogenesis in motor cortex infarction in rats. (2017)
  • Author(s): Kumada T, Morishita S, Hokamura K, Yoshikawa A, Agata N, Tsutsui Y and Umemura K.
  • Organizer: The 41st Annual Meeting, Society for Neuroscience
  • Int'l Joint Research
• [Book] Granule Cell Migration and Differentiation, In: Manto M., Gruol D., Schmahmann J., Koibuchi N., Sillitoe R. (eds) (2021)
  • Author(s): Komuro, Y., Fahrion, J. F., Foote, K.D., Fenner K. B., Kumada, T., Ohno, N., and Komuro, H.
  • Total Pages: 33
  • Publisher: Springer
  • ISBN: 9783030238094
• [Book] Multimodal GABAA receptor functions in the development of the central nervous system. “Synapse Development and Maturation” In: Comprehensive Developmental Neuroscience, (Rubenstein, J., Rakic, P., eds) (2020)
  • Author(s): Kumada, T., and Fukuda, A
  • Total Pages: 21
  • Publisher: Academic press
  • ISBN: 9780128236727