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

A Schmidt-Pogoda; T Ruck; J K 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; A M 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; S G Meuth; J Minnerup

doi:10.1038/s41467-025-62631-y

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

Nat Commun. 2025 Oct 8;16(1):8928. doi: 10.1038/s41467-025-62631-y.

Authors

A Schmidt-Pogoda¹, T Ruck^{2

3}, J K Strecker^{4

5}, M Hoppen⁴, L Fazio⁶, L Vinnenberg⁶, B Maus⁷, L Wachsmuth⁷, M Cerina⁴, K Diederich⁴, S Lichtenberg⁵, H Abberger^{8

9

10}, Lal Haertel⁴, D Schafflick^{4

11}, G Meyer Zu Hörste⁴, A M Herrmann⁶, P Hundehege⁴, V Narayanan⁴, C Nelke⁶, K Kruithoff⁴, J Bosbach⁴, E Vicari¹², T Ramcke¹², C Beuker⁴, E Hadaschik¹², T Budde¹³, C Faber⁷, H Wiendl^{4

11}, W Hansen⁸, S G Meuth⁶, J Minnerup^{14

15}

Affiliations

¹ Department of Neurology, University of Münster, Münster, Germany. antje.schmidt-pogoda@ukmuenster.de.
² Department of Neurology, Ruhr University Bochum, BG University Hospital Bergmannsheil, Bochum, Germany.
³ Heimer Institute for Muscle Research, BG University Hospital Bergmannsheil, Bochum, Germany.
⁴ Department of Neurology, University of Münster, Münster, Germany.
⁵ Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany.
⁶ Department of Neurology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
⁷ Clinic of Radiology, University of Münster, Münster, Germany.
⁸ Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
⁹ Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
¹⁰ Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
¹¹ Department of Neurology and Neurophysiology, University Hospital Freiburg, Freiburg, Germany.
¹² Department of Dermatology, Heidelberg University Hospital, Heidelberg, Germany.
¹³ Institute of Physiology I, University of Münster, Münster, Germany.
¹⁴ Department of Neurology, University of Münster, Münster, Germany. minnerup@uni-muenster.de.
¹⁵ Department of Neurology, University of Lübeck and University Hospital Schleswig-Holstein, Lübeck, Germany. minnerup@uni-muenster.de.

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.

MeSH terms

Animals
Brain / pathology
Brain / physiopathology
Brain Ischemia / immunology
Brain Ischemia / physiopathology
Disease Models, Animal
Interleukin-10* / genetics
Interleukin-10* / metabolism
Ischemic Stroke* / immunology
Ischemic Stroke* / physiopathology
Male
Mice
Mice, Inbred C57BL
Neurons* / metabolism
Neurons* / physiology
Physical Conditioning, Animal* / physiology
Recovery of Function
Signal Transduction
Stroke Rehabilitation* / methods
Stroke* / immunology
Stroke* / physiopathology
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism

Substances

Interleukin-10
IL10 protein, mouse

Abstract

MeSH terms

Substances

Grants and funding