TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage
Author(s)
Taylor, Roslyn A.; Chang, Che-Feng; Hammond, Matthew D.; Grory, Brian Mac; Ai, Youxi; Steinschneider, Arthur F.; Renfroe, Stephen C.; Askenase, Michael H.; McCullough, Louise D.; Kasner, Scott E.; Mullen, Michael T.; Hafler, David A.; Sansing, Lauren H.; Love, John C; Goods, Brittany A.; ... Show more Show less
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Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from the rupture of a blood vessel in the brain, leading to a mass of blood within the brain parenchyma. The injury causes a rapid inflammatory reaction that includes activation of the tissue-resident microglia and recruitment of blood-derived macrophages and other leukocytes. In this work, we investigated the specific responses of microglia following ICH with the aim of identifying pathways that may aid in recovery after brain injury. We used longitudinal transcriptional profiling of microglia in a murine model to determine the phenotype of microglia during the acute and resolution phases of ICH in vivo and found increases in TGF-β1 pathway activation during the resolution phase. We then confirmed that TGF-β1 treatment modulated inflammatory profiles of microglia in vitro. Moreover, TGF-β1 treatment following ICH decreased microglial Il6 gene expression in vivo and improved functional outcomes in the murine model. Finally, we observed that patients with early increases in plasma TGF-β1 concentrations had better outcomes 90 days after ICH, confirming the role of TGF-β1 in functional recovery from ICH. Taken together, our data show that TGF-β1 modulates microglia-mediated neuroinflammation after ICH and promotes functional recovery, suggesting that TGF-β1 may be a therapeutic target for acute brain injury.
Date issued
2016-11Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Chemical Engineering; Koch Institute for Integrative Cancer Research at MITJournal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Citation
Taylor, Roslyn A.; Chang, Che-Feng; Goods, Brittany A.; Hammond, Matthew D.; Grory, Brian Mac; Ai, Youxi; Steinschneider, Arthur F. et al. “TGF-Β1 Modulates Microglial Phenotype and Promotes Recovery after Intracerebral Hemorrhage.” Journal of Clinical Investigation 127, no. 1 (January 2017): 280–292 © 2017 American Society for Clinical Investigation
Version: Final published version
ISSN
0021-9738
1558-8238