| First Author | Taylor RA | Year | 2017 |
| Journal | J Clin Invest | Volume | 127 |
| Issue | 1 | Pages | 280-292 |
| PubMed ID | 27893460 | Mgi Jnum | J:239742 |
| Mgi Id | MGI:5829594 | Doi | 10.1172/JCI88647 |
| Citation | Taylor RA, et al. (2017) TGF-beta1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J Clin Invest 127(1):280-292 |
| abstractText | 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-beta1 pathway activation during the resolution phase. We then confirmed that TGF-beta1 treatment modulated inflammatory profiles of microglia in vitro. Moreover, TGF-beta1 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-beta1 concentrations had better outcomes 90 days after ICH, confirming the role of TGF-beta1 in functional recovery from ICH. Taken together, our data show that TGF-beta1 modulates microglia-mediated neuroinflammation after ICH and promotes functional recovery, suggesting that TGF-beta1 may be a therapeutic target for acute brain injury. |
