title: Toll-like receptor-4-mediated autophagy contributes to microglial activation and inflammatory injury in mouse models of intracerebral haemorrhage.
abstract: OBJECTIVE
  Much evidence demonstrates that Toll-like receptor-4 (TLR4)-mediated microglial activation is an important contributor to the inflammatory injury in intracerebral haemorrhage (ICH). However, the exact mechanism of TLR4-mediated microglial activation induced by ICH is not clear. In addition, microglial autophagy is involved other forms of nervous system injury. To explore the relationship between TLR4 and autophagy, we investigated the role of TLR4-mediated microglial autophagy and inflammation in ICH.
  
  
  METHODS
  We detected TLR4 expression, autophagy and inflammation of microglia treated with lysed erythrocytes in vitro, and observed the cerebral water content and neurological deficit of ICH mice [TLR4-/- and wild type (WT)] in vivo.
  
  
  RESULTS
  We found that lysed erythrocyte treated microglia (TLR4-/-) had reduced autophagy and inflammation compared with microglia (WT) in vitro. ICH mice (TLR4-/-) had reduced water content and neurological injury compared with ICH mice (WT). The autophagy inhibitor (3-methyladenine) decreased microglial activation and inflammatory injury due to lysed erythrocyte treatment, and improved the neurological function of ICH mice.
  
  
  CONCLUSIONS
  Taken together, these data suggested that TLR4 induced autophagy contributed to the microglial activation and inflammatory injury and might provide novel therapeutic interventions for ICH.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing.
authors.forename: L
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian.
authors.forename: Hanchao
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian.
authors.forename: Chuangan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001343:Autophagy; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000150:complications / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
keywords: ICH; TLR4; autophagy; microglia