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; L. A.L. 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

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, L. A.L. Haertel, D. Schafflick, G. Meyer zu Hörste, A. M. Herrmann, P. Hundehege, V. Narayanan, C. Nelke, K. KruithoffJ. Bosbach, E. Vicari, T. Ramcke, C. Beuker, E. Hadaschik, T. Budde, C. Faber, H. Wiendl, W. Hansen, S. G. Meuth, J. Minnerup^*

^*Corresponding author for this work

Department of Neurology

3 Citations (Scopus)

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.

Original language	English
Article number	8928
Journal	Nature Communications
Volume	16
Issue number	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-025-62631-y
Publication status	Published - 12.2025

Funding

Funders	Funder number
Deutsche Forschungsgemeinschaft	428668629, 405358801, FOR 2879, 507892174, GRK 2515

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

DFG Research Classification Scheme

2.23-07 Clinical Neurology, Neurosurgery and Neuroradiology

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Schmidt-Pogoda, A., Ruck, T., Strecker, J. K., Hoppen, M., Fazio, L., Vinnenberg, L., Maus, B., Wachsmuth, L., Cerina, M., Diederich, K., Lichtenberg, S., Abberger, H., Haertel, L. A. L., Schafflick, D., Meyer zu Hörste, G., Herrmann, A. M., Hundehege, P., Narayanan, V., Nelke, C., ... Minnerup, J. (2025). Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling. Nature Communications, 16(1), Article 8928. https://doi.org/10.1038/s41467-025-62631-y

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title = "Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling",

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.",

author = "A. Schmidt-Pogoda and T. Ruck and Strecker, \{J. K.\} and M. Hoppen and L. Fazio and L. Vinnenberg and B. Maus and L. Wachsmuth and M. Cerina and K. Diederich and S. Lichtenberg and H. Abberger and Haertel, \{L. A.L.\} and D. Schafflick and \{Meyer zu H{\"o}rste\}, G. and Herrmann, \{A. M.\} and P. Hundehege and V. Narayanan and C. Nelke and K. Kruithoff and J. Bosbach and E. Vicari and T. Ramcke and C. Beuker and E. Hadaschik and T. Budde and C. Faber and H. Wiendl and W. Hansen and Meuth, \{S. G.\} and J. Minnerup",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41467-025-62631-y",

language = "English",

volume = "16",

journal = "Nature Communications",

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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, LAL, 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 2025, 'Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling', Nature Communications, vol. 16, no. 1, 8928. https://doi.org/10.1038/s41467-025-62631-y

TY - JOUR

T1 - Exercise facilitates post-stroke recovery through mitigation of neuronal hyperexcitability via interleukin-10 signaling

AU - Schmidt-Pogoda, A.

AU - Ruck, T.

AU - Strecker, J. K.

AU - Hoppen, M.

AU - Fazio, L.

AU - Vinnenberg, L.

AU - Maus, B.

AU - Wachsmuth, L.

AU - Cerina, M.

AU - Diederich, K.

AU - Lichtenberg, S.

AU - Abberger, H.

AU - Haertel, L. A.L.

AU - Schafflick, D.

AU - Meyer zu Hörste, G.

AU - Herrmann, A. M.

AU - Hundehege, P.

AU - Narayanan, V.

AU - Nelke, C.

AU - Kruithoff, K.

AU - Bosbach, J.

AU - Vicari, E.

AU - Ramcke, T.

AU - Beuker, C.

AU - Hadaschik, E.

AU - Budde, T.

AU - Faber, C.

AU - Wiendl, H.

AU - Hansen, W.

AU - Meuth, S. G.

AU - Minnerup, J.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105018266981

U2 - 10.1038/s41467-025-62631-y

DO - 10.1038/s41467-025-62631-y

M3 - Journal articles

C2 - 41062473

AN - SCOPUS:105018266981

SN - 1751-8628

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 8928

ER -

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

Abstract

Funding

UN SDGs

DFG Research Classification Scheme

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