• Guohua Wang, Jia Zhang, Xiaoming Hu, Lili Zhang, Leilei Mao, Xiaoyan Jiang, Anthony Kian-Fong Liou, Rehana K Leak, Yanqin Gao, and Jun Chen.
• 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.
• J. Cereb. Blood Flow Metab. 2013 Dec 1; 33 (12): 1864-74.

AbstractMononuclear 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.

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