Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut– brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut– brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed that SCFAs induced altered contralesional cortex connectivity. This was associated with SCFA-dependent changes in spine and synapse densities. RNA sequencing of the forebrain cortex indicated a potential involvement of microglial cells in contributing to the structural and functional remodeling. Further analyses confirmed a substantial impact of SCFAs on microglial activation, which depended on the recruitment of T cells to the infarcted brain. Our findings identified that microbiota-derived SCFAs modulate poststroke recovery via effects on systemic and brain resident immune cells.
|Number of pages||12|
|Journal||Journal of Neuroscience|
|State||Published - Jan 29 2020|
Bibliographical noteFunding Information:
ThisworkwassupportedbytheGermanResearchFoundation(DeutscheForschungsgemeinschaft,LI2534/2-1), the European Research Council (ERC-StG 802305), the Vascular Dementia Research Foundation, and the Munich Cluster for Systems Neurology (EXC 2145 SyNergy) ID 390857198 to A.L., the Texas Institute for Brain Injury and
This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, LI2534/2-1), the European Research Council (ERC-StG 802305), the Vascular Dementia Research Foundation, and the Munich Cluster for Systems Neurology (EXC 2145 SyNergy) ID 390857198 to A.L., the Texas Institute for Brain Injury and Repair to M.P.G. and A.M.S., and National Institutes of Health/National Institute of Neurological Disorders and Stroke (NS088555) to A.M.S. We thank Kerstin Thu?-Silczak for excellent technical assistance.
Copyright © 2020 the authors
- Stroke models
ASJC Scopus subject areas
- Neuroscience (all)