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

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 strok...

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Bibliographic Details
Published in:Nature communications Vol. 16; no. 1; pp. 8928 - 16
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 08.10.2025
Nature Publishing Group
Nature Portfolio
Subjects:
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13/106
13/31
13/51
14/19
14/34
14/35
14/63
38/77
59
59/57
64/110
692/617/375/380
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Adhesives
Animals
Asymmetry
Brain - pathology
Brain - physiopathology
Brain Ischemia - immunology
Brain Ischemia - physiopathology
Cytokines
Disease Models, Animal
Exercise
Humanities and Social Sciences
Immune system
Immunoregulation
Interleukin 10
Interleukin-10 - genetics
Interleukin-10 - metabolism
Interleukins
Ischemia
Ischemic Stroke - immunology
Ischemic Stroke - physiopathology
Lymphocytes
Lymphocytes T
Magnetic resonance imaging
Male
Mice
Mice, Inbred C57BL
Molecular modelling
multidisciplinary
Neural networks
Neurons - metabolism
Neurons - physiology
Neuroplasticity
Physical Conditioning, Animal - physiology
Physical exercise
Recovery
Recovery of Function
Regeneration
Science
Science (multidisciplinary)
Signal Transduction
Stroke
Stroke - immunology
Stroke - physiopathology
Stroke Rehabilitation - methods
Structure-function relationships
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Exercise promotes recovery after stroke, but the underlying mechanisms are unclear. Here, the authors show that regulatory T cells enable exercise-induced repair by reducing neuronal hyperexcitability via interleukin-10, linking immunity to functional regeneration.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-62631-y