Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling
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.
Authors
- Cornelius Faber (ORCID: https://orcid.org/0000-0001-7683-7710)
- E. Hadaschik
- Laura Vinnenberg (ORCID: https://orcid.org/0000-0001-8843-007X)
- Manuela Cerina (ORCID: https://orcid.org/0000-0001-7888-6436)
- Lisa K. Fazio (ORCID: https://orcid.org/0000-0002-0415-4862)
- David Schafflick (ORCID: https://orcid.org/0000-0001-5908-4745)
- Sven Guenther Meuth (ORCID: https://orcid.org/0000-0003-2571-3501)
- Heinz Wiendl (ORCID: https://orcid.org/0000-0003-4310-3432)
- Bastian Maus (ORCID: https://orcid.org/0000-0003-1872-9097)
- Maike Hoppen (ORCID: https://orcid.org/0000-0002-7921-8322)
- Petra Hundehege (ORCID: https://orcid.org/0000-0001-9562-0285)
- Hanna Abberger
- Tobias Ruck (ORCID: https://orcid.org/0000-0001-6332-8650)
- JK Strecker
- Vinodh Narayanan (ORCID: https://orcid.org/0000-0002-0658-3847)
- Lydia Wachsmuth (ORCID: https://orcid.org/0000-0003-1684-7196)
- Stefanie Lichtenberg (ORCID: https://orcid.org/0000-0003-4703-2571)
- Thomas Budde (ORCID: https://orcid.org/0000-0002-5263-8183)
- T. Ramcke
- Wiebke Hansen (ORCID: https://orcid.org/0000-0002-6020-0886)
- Christopher Nelke (ORCID: https://orcid.org/0000-0002-6048-7143)
- Kai Diederich (ORCID: https://orcid.org/0000-0002-6550-9460)
- E. Vicari
- Antje Schmidt‐Pogoda (ORCID: https://orcid.org/0000-0002-0389-6389)
- Gerd Meyer zu Hörste (ORCID: https://orcid.org/0000-0002-4341-4719)
- Carolin Beuker (ORCID: https://orcid.org/0000-0003-3495-0357)
- Jens Minnerup (ORCID: https://orcid.org/0000-0002-0382-5759)
- Alexander M. Herrmann (ORCID: https://orcid.org/0000-0001-7029-1032)
- LAL Haertel
- K. Kruithoff
- J. Bosbach
Institutions
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Heidelberg University (DE)
- University of Münster (DE)
- University Medical Center Freiburg (DE)
- University Hospital Heidelberg (DE)
- University Hospital Münster (DE)
- University Hospital Schleswig-Holstein (DE)
- BG University Hospital Bergmannsheil Bochum (DE)
- Heinrich Heine University Düsseldorf (DE)
- University of Duisburg-Essen (DE)
- FH Münster University of Applied Sciences (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-08
- DOI
- https://doi.org/10.1038/s41467-025-62631-y
- Citations
- 2
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.68