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Role of microglia autophagy in microglia activation after traumatic brain injury.
World Neurosurg. 2017 Jan 17;:
Authors: Jin Y, Wang R, Yang S, Zhang X, Dai J
Abstract
OBJECTIVE: Role of microglia autophagy in microglia activation after traumatic brain injury (TBI) remains elusive. Here, we evaluated role of microglia autophagy in microglia activation after traumatic brain injury (TBI) in rats.
METHODS: TBI was induced by a fluid percussion TBI device. All rats were killed at 24 h after TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; Immunohistochemistry and western blotting of IBA-1 was used to determine the changes of microglia activation; Double staining of microtubule-associated protein light chain 3 (LC-3), Beclin-1 and IBA-1 was used to assess the changes of microglia autophagy; enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor receptor-alpha (TNF-α) and interleukin-1β (IL-1β) was used to evaluate the changes of inflammatory responses; terminal deoxynucleoitidyl transferase mediated nick end labeling staining (TUNEL) was used to determine cell death in ipsilateral hippocampus.
RESULTS: At 24 h after TBI, microglial cells become activated and autophagy inhibitor, 3-MA, could further promote microglia activation. LC3- and Beclin-1- positive microglial cells were increased after TBI while 3-MA decreased the number of positive microglial cells, thus increasing the expression of TNF-α and IL-1; TUNEL staining demonstrated that 3-MA could increase the number of TUNEL-positive cells (16.83±0.83 vs 11±0.82, p<0.001).
CONCLUSION: Our data demonstrated that TBI could induce microglia activation and microglia autophagy. Inhibition of microglia autophagy with 3-MA could increase the microglia activation and neural apoptosis which indicated that targeting microglia autophagy may be a therapeutic strategy for TBI.
PMID: 28108422 [PubMed - as supplied by publisher]
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