title: Role of Microglia Autophagy in Microglia Activation After Traumatic Brain Injury.
abstract: OBJECTIVE
  We evaluated the 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 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.
  
  
  RESULTS
  At 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).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China. Electronic address: zhangxh1969@hotmail.com.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China. Electronic address: jiongdai@hotmail.com.
authors.forename: Jiong
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018836:Inflammation Mediators
keywords: Apoptosis; Autophagy; Microglia; Traumatic brain injury