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

A. Schmidt-Pogoda (), T. Ruck, Strecker Jk, M. Hoppen, L. Fazio, L. Vinnenberg, B. Maus, L. Wachsmuth, M. Cerina, K. Diederich, S. Lichtenberg, H. Abberger, Haertel Lal, D. Schafflick, G. Meyer zu Hörste, Herrmann Am, P. Hundehege, V. Narayanan, C. Nelke, K. Kruithoff, J. Bosbach, E. Vicari, T. Ramcke, C. Beuker, E. Hadaschik, T. Budde, C. Faber, H. Wiendl, W. Hansen, Meuth Sg and J. Minnerup ()
Additional contact information
A. Schmidt-Pogoda: University of Münster
T. Ruck: Ruhr University Bochum, BG University Hospital Bergmannsheil
Strecker Jk: University of Münster
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
Haertel Lal: University of Münster
D. Schafflick: University of Münster
G. Meyer zu Hörste: University of Münster
Herrmann Am: 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
W. Hansen: University Duisburg-Essen
Meuth Sg: Heinrich-Heine-University
J. Minnerup: University of Münster

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62631-y

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