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Microglia/macrophage polarization dynamics in white matter after traumatic brain injury.
J Cereb Blood Flow Metab. 2013 Dec; 33(12):1864-74.JC

Abstract

Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.

Authors+Show Affiliations

1] State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, Shanghai, China [2] Department of Neurology, Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA [3] Department of Neuropharmacology, Institute of Nautical Medicine, Nantong University, Nantong, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23942366

Citation

Wang, Guohua, et al. "Microglia/macrophage Polarization Dynamics in White Matter After Traumatic Brain Injury." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 33, no. 12, 2013, pp. 1864-74.
Wang G, Zhang J, Hu X, et al. Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. J Cereb Blood Flow Metab. 2013;33(12):1864-74.
Wang, G., Zhang, J., Hu, X., Zhang, L., Mao, L., Jiang, X., Liou, A. K., Leak, R. K., Gao, Y., & Chen, J. (2013). Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 33(12), 1864-74. https://doi.org/10.1038/jcbfm.2013.146
Wang G, et al. Microglia/macrophage Polarization Dynamics in White Matter After Traumatic Brain Injury. J Cereb Blood Flow Metab. 2013;33(12):1864-74. PubMed PMID: 23942366.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microglia/macrophage polarization dynamics in white matter after traumatic brain injury. AU - Wang,Guohua, AU - Zhang,Jia, AU - Hu,Xiaoming, AU - Zhang,Lili, AU - Mao,Leilei, AU - Jiang,Xiaoyan, AU - Liou,Anthony Kian-Fong, AU - Leak,Rehana K, AU - Gao,Yanqin, AU - Chen,Jun, Y1 - 2013/08/14/ PY - 2013/03/29/received PY - 2013/07/12/revised PY - 2013/07/15/accepted PY - 2013/8/15/entrez PY - 2013/8/15/pubmed PY - 2014/2/4/medline SP - 1864 EP - 74 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 33 IS - 12 N2 - Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment. SN - 1559-7016 UR - https://www.unboundmedicine.com/medline/citation/23942366/Microglia/macrophage_polarization_dynamics_in_white_matter_after_traumatic_brain_injury_ L2 - https://journals.sagepub.com/doi/10.1038/jcbfm.2013.146?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -