Microglia/macrophage polarization dynamics in white matter after traumatic brain injury.
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.
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.
Guohua
G
Wang
Jia
J
Zhang
Xiaoming
X
Hu
Lili
L
Zhang
Leilei
L
Mao
Xiaoyan
X
Jiang
Anthony Kian-Fong
AK
Liou
Rehana K
RK
Leak
Yanqin
Y
Gao
Jun
J
Chen
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D005947:Glucose; D010100:Oxygen