TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage
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 recruitme...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Society for Clinical Investigation
2017
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| Online Access: | http://hdl.handle.net/1721.1/109762 https://orcid.org/0000-0003-0921-3144 |
| _version_ | 1811088092484861952 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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. |
| author_sort | Taylor, Roslyn A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T13:56:08Z |
| format | Article |
| id | mit-1721.1/109762 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:56:08Z |
| publishDate | 2017 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | mit-1721.1/1097622022-09-28T17:12:59Z TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage 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. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Love, John C Goods, Brittany A. 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. 2017-06-09T13:33:24Z 2017-06-09T13:33:24Z 2016-11 2016-05 Article http://purl.org/eprint/type/JournalArticle 0021-9738 1558-8238 http://hdl.handle.net/1721.1/109762 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 https://orcid.org/0000-0003-0921-3144 en_US http://dx.doi.org/10.1172/jci88647 Journal of Clinical Investigation Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Society for Clinical Investigation American Society for Clinical Investigation |
| spellingShingle | 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. TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title | TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title_full | TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title_fullStr | TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title_full_unstemmed | TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title_short | TGF-β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| title_sort | tgf β1 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage |
| url | http://hdl.handle.net/1721.1/109762 https://orcid.org/0000-0003-0921-3144 |
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