• Yichao Jin, Ran Wang, Shaofeng Yang, Xiaohua Zhang, and Jiong Dai.
• Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
• World Neurosurg. 2017 Apr 1; 100: 351-360.

ObjectiveWe evaluated the role of microglia autophagy in microglia activation after traumatic brain injury (TBI) in rats.MethodsTBI was induced by a fluid percussion TBI device. All rats were killed 24 hours after TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin-eosin staining. Immunohistochemistry and Western blotting of ionized calcium-binding adapter molecule 1 was used to determine changes in microglia activation. Double staining of microtubule-associated protein light chain 3, Beclin-1, and ionized calcium-binding adapter molecule 1 was used to assess changes of microglia autophagy. Enzyme-linked immunosorbent assay of tumor necrosis factor-α and interleukin-1β was used to evaluate changes in inflammatory responses. Terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining was used to determine cell death in the ipsilateral hippocampus.ResultsAt 24 hours after TBI, microglial cells became activated, and the autophagy inhibitor 3-methyladenine (3-MA) further promoted microglia activation. Protein light chain 3- and Beclin-1-positive microglial cells were increased after TBI, whereas 3-MA decreased the number of positive microglial cells, increasing the expression of tumor necrosis factor-α and interleukin-1β; terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining demonstrated that 3-MA could increase the number of terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling-positive cells (16.83 ± 0.83 vs. 11 ± 0.82, P < 0.001).ConclusionsOur data demonstrated that TBI induced microglia activation and microglia autophagy. Inhibition of microglia autophagy with 3-MA increased microglia activation and neural apoptosis. These findings indicate that targeting microglia autophagy may be a therapeutic strategy for TBI.Copyright © 2017 Elsevier Inc. All rights reserved.

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