期刊
JOURNAL OF NEUROTRAUMA
卷 35, 期 19, 页码 2330-2340出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2017.5540
关键词
axonal injury; microglia; neuroinflammation; peroxisome proliferator-activated receptor gamma (PPAR-gamma); polarization
资金
- Natural Science Foundation of Zhejiang Province [LY15H090005]
- National Natural Science Foundation of China [81200955, 31371406, 81771317]
- SMC-Star Award for Young Scholars
Increasing evidence indicates that activated microglia play an important role in the inflammatory response following traumatic brain injury (TBI). Inhibiting M1 and stimulating M2 activated microglia have demonstrated protective effects in several animal models of central nervous system diseases. However, it is not clear whether the polarization of microglia to M2 attenuates axonal injury following TBI. In this study, we used a lateral fluid percussion injury device to induce axonal injury in mice. Mice were randomly assigned to the sham, TBI, TBI + rosiglitazone (peroxisome proliferator-activated receptor gamma [PPAR-gamma] agonist), and TBI + GW9662 (PPAR-gamma antagonist) groups. Axonal injury was assessed using immunohistochemical staining for beta amyloid precursor protein. The inflammatory response was assessed by enzyme-linked immunosorbent assay, microglia polarization was assessed using specific markers of M1 and M2 microglia, and neurological function was assessed using the neurological severity score. Following TBI, microglia of the M1 phenotype increased significantly, while those of the M2 phenotype decreased. Rosiglitazone-induced PPAR-gamma activation promoted microglia polarization to the M2 phenotype, which reduced the inflammatory response, attenuated axonal injury in the cerebral cortex, and improved neurological function. Conversely, GW9662 inhibited the polarization of microglia to M2 and aggravated inflammation and axonal injury. Our in vitro findings in lipopolysaccharide-induced microglia were consistent with those of our in vivo experiments. In conclusion, the polarization of microglia to the M2 phenotype via PPAR-gamma activation attenuated axonal injury following TBI in mice, which may be a potential therapeutic approach for TBI-induced axonal injury.
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