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

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

Abstract

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published October 08, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (31)

A

A. Schmidt-Pogoda

T

T. Ruck

J

JK Strecker

M

M. Hoppen

L

L. Fazio

L

L. Vinnenberg

B

B. Maus

L

L. Wachsmuth

M

M. Cerina

K

K. Diederich

S

S. Lichtenberg

H

H. Abberger

L

LAL Haertel

D

D. Schafflick

G

G. Meyer zu Hörste

A

AM Herrmann

P

P. Hundehege

V

V. Narayanan

C

C. Nelke

K

K. Kruithoff

J

J. Bosbach

E

E. Vicari

T

T. Ramcke

C

C. Beuker

E

E. Hadaschik

T

T. Budde

C

C. Faber

H

H. Wiendl

W

W. Hansen

S

SG Meuth

J

J. Minnerup