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Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling

Author

Listed:
  • A. Schmidt-Pogoda

    (University of Münster)

  • T. Ruck

    (Ruhr University Bochum, BG University Hospital Bergmannsheil
    BG University Hospital Bergmannsheil)

  • JK Strecker

    (University of Münster
    University of Lübeck and University Hospital Schleswig-Holstein)

  • M. Hoppen

    (University of Münster)

  • L. Fazio

    (Heinrich-Heine-University)

  • L. Vinnenberg

    (Heinrich-Heine-University)

  • B. Maus

    (University of Münster)

  • L. Wachsmuth

    (University of Münster)

  • M. Cerina

    (University of Münster)

  • K. Diederich

    (University of Münster)

  • S. Lichtenberg

    (University of Lübeck and University Hospital Schleswig-Holstein)

  • H. Abberger

    (University Duisburg-Essen
    Walter and Eliza Hall Institute of Medical Research
    University of Melbourne)

  • LAL Haertel

    (University of Münster)

  • D. Schafflick

    (University of Münster
    University Hospital Freiburg)

  • G. Meyer zu Hörste

    (University of Münster)

  • AM Herrmann

    (Heinrich-Heine-University)

  • P. Hundehege

    (University of Münster)

  • V. Narayanan

    (University of Münster)

  • C. Nelke

    (Heinrich-Heine-University)

  • K. Kruithoff

    (University of Münster)

  • J. Bosbach

    (University of Münster)

  • E. Vicari

    (Heidelberg University Hospital)

  • T. Ramcke

    (Heidelberg University Hospital)

  • C. Beuker

    (University of Münster)

  • E. Hadaschik

    (Heidelberg University Hospital)

  • T. Budde

    (University of Münster)

  • C. Faber

    (University of Münster)

  • H. Wiendl

    (University of Münster
    University Hospital Freiburg)

  • W. Hansen

    (University Duisburg-Essen)

  • SG Meuth

    (Heinrich-Heine-University)

  • J. Minnerup

    (University of Münster
    University of Lübeck and University Hospital Schleswig-Holstein)

Abstract

Physical exercise is an effective therapy for improving stroke recovery. However, the exact underlying molecular mechanisms of exercise-enhanced neuronal repair remain unclear. As exercise affects the immune system in healthy individuals, and the immune system in turn influences recovery after stroke, we hypothesized that immune mechanisms play a role in exercise-induced neurological recovery. Using a model of ischemic stroke in adult male mice, we here show that the presence of regulatory T cells (Treg) within the ischemic brain is a prerequisite for exercise-enhanced functional and structural recovery. Treg prevent excessive and sustained hyperexcitability of periinfarct neurons via IL-10 signaling. This reduced hyperexcitability precedes alterations in neuronal connectivity, which underlie functional improvement. Together, we delineate the interaction of exercise-therapy, the immune system and functional recovery after ischemic stroke. Our findings can have translational relevance for further development of immune-targeted therapies.

Suggested Citation

  • A. Schmidt-Pogoda & T. Ruck & JK Strecker & M. Hoppen & L. Fazio & L. Vinnenberg & B. Maus & L. Wachsmuth & M. Cerina & K. Diederich & S. Lichtenberg & H. Abberger & LAL Haertel & D. Schafflick & G. M, 2025. "Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62631-y
    DOI: 10.1038/s41467-025-62631-y
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    References listed on IDEAS

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    1. Ke Cheng & Deliang Shen & M. Taylor Hensley & Ryan Middleton & Baiming Sun & Weixin Liu & Geoffrey De Couto & Eduardo Marbán, 2014. "Magnetic antibody-linked nanomatchmakers for therapeutic cell targeting," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    2. Federico Scala & Dmitry Kobak & Matteo Bernabucci & Yves Bernaerts & Cathryn René Cadwell & Jesus Ramon Castro & Leonard Hartmanis & Xiaolong Jiang & Sophie Laturnus & Elanine Miranda & Shalaka Mulher, 2021. "Phenotypic variation of transcriptomic cell types in mouse motor cortex," Nature, Nature, vol. 598(7879), pages 144-150, October.
    3. Anthony J. Filiano & Yang Xu & Nicholas J. Tustison & Rachel L. Marsh & Wendy Baker & Igor Smirnov & Christopher C. Overall & Sachin P. Gadani & Stephen D. Turner & Zhiping Weng & Sayeda Najamussahar , 2016. "Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour," Nature, Nature, vol. 535(7612), pages 425-429, July.
    4. Shane A. Liddelow & Kevin A. Guttenplan & Laura E. Clarke & Frederick C. Bennett & Christopher J. Bohlen & Lucas Schirmer & Mariko L. Bennett & Alexandra E. Münch & Won-Suk Chung & Todd C. Peterson & , 2017. "Neurotoxic reactive astrocytes are induced by activated microglia," Nature, Nature, vol. 541(7638), pages 481-487, January.
    5. Andrew N. Clarkson & Ben S. Huang & Sarah E. MacIsaac & Istvan Mody & S. Thomas Carmichael, 2010. "Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke," Nature, Nature, vol. 468(7321), pages 305-309, November.
    6. Minako Ito & Kyoko Komai & Setsuko Mise-Omata & Mana Iizuka-Koga & Yoshiko Noguchi & Taisuke Kondo & Ryota Sakai & Kazuhiko Matsuo & Takashi Nakayama & Osamu Yoshie & Hiroko Nakatsukasa & Shunsuke Chi, 2019. "Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery," Nature, Nature, vol. 565(7738), pages 246-250, January.
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