Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling
Antje Schmidt‐Pogoda, Tobias Ruck, JK Strecker, Maike Hoppen, Lisa K. Fazio, Laura Vinnenberg, Bastian Maus, Lydia Wachsmuth, Manuela Cerina, Kai Diederich, Stefanie Lichtenberg, Hanna Abberger, LAL Haertel, David Schafflick, Gerd Meyer zu Hörste, Alexander M. Herrmann, Petra Hundehege, Vinodh Narayanan, Christopher Nelke, K. Kruithoff, J. Bosbach, E. Vicari, T. Ramcke, Carolin Beuker, E. Hadaschik, Thomas Budde, Cornelius Faber, Heinz Wiendl, Wiebke Hansen, Sven G. Meuth, Jens Minnerup
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.