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

Schmidt-Pogoda A; Ruck T; Strecker JK; Hoppen M; Fazio L; Vinnenberg L; Maus B; Wachsmuth L; Cerina M; Diederich K; Lichtenberg S; Abberger H; Haertel L; Schafflick D; Meyer Zu Hörste G; Herrmann AM; Hundehege P; Narayanan V; Nelke C; Kruithoff K; Bosbach J; Vicari E; Ramcke T; Beuker C; Hadaschik E; Budde T; Faber C; Wiendl H; Hansen W; Meuth SG; Minnerup J

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.