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^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Klinik für Neurologie

4 Zitate (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.

Originalsprache	Englisch
Aufsatznummer	8928
Zeitschrift	Nature Communications
Jahrgang	16
Ausgabenummer	1
ISSN	1751-8628
DOIs	https://doi.org/10.1038/s41467-025-62631-y
Publikationsstatus	Veröffentlicht - 12.2025

Fördermittel

This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG) – FOR 2879 (ID 405358801, 428668629 and 507892174) and DFG Research Training Group GRK 2515. We thank Birgit Schmeddes and Sina Luppus for excellent technical assistance and Klaus Lennartz for single-cell sorting.

Träger	Trägernummer
Deutsche Forschungsgemeinschaft	428668629, 405358801, FOR 2879, 507892174, GRK 2515

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SDG 3 – Gesundheit und Wohlergehen

DFG-Fachsystematik

2.23-07 Klinische Neurologie, Neurochirurgie und Neuroradiologie

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10.1038/s41467-025-62631-y

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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), Artikel 8928. https://doi.org/10.1038/s41467-025-62631-y

@article{0cafa245b6a340c9948407cf36309fa3,

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",

issn = "1751-8628",

publisher = "John Wiley \& Sons Inc.",

number = "1",

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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, Jg. 16, Nr. 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

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