Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling
- 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. Meyer zu Hörste
- AM Herrmann
- 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
- SG Meuth
- J. Minnerup
2025-10-08
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.