title: N-methyl-D-aspartic acid receptor 1 (NMDAR1) aggravates secondary inflammatory damage induced by hemin-NLRP3 pathway after intracerebral hemorrhage.
abstract: OBJECTIVE
  Inflammation plays a critical role in secondary brain damage after intracerebral hemorrhage (ICH). However, the mechanisms of inflammatory injury following ICH are still unclear, particularly the involvement of NLRP3 inflammasome, which are crucial to sterile inflammatory responses. In this study, we aim to test the hypothesis that NLRP3 signaling pathway takes a vital position in ICH-induced secondary inflammatory damage and detect the role of N-methyl-D-aspartic acid receptor 1 (NMDAR1) in this progress.
  
  
  METHODS
  ICH was induced in mice by microinjection of hemin into the striatum. The protein levels of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were measured by Western blot. The binding of NMDAR1 to NLRP3 was detected by immunoprecipitation.
  
  
  RESULTS
  The expression of NMDAR1, NMDAR1 phosphorylation, NLRP3 and IL-1b were rapidly increased after ICH. Hemin treatment enhanced NMDAR1 expression and NMDAR1 phosphorylation, as well in cultured microglial cells treated by hemin. Hemin up regulated NLRP3 and IL-1b level, which was reversed by MK801 (NMDAR antagonist) in vitro. Hemin also promoted the binding of NMDAR1 to NLRP3.
  
  
  CONCLUSIONS
  Our findings suggest that NMDAR1 plays a pivotal role in hemin-induced NLRP3-mediated inflammatory damage through synergistic activation.
authors.affiliation: State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery/Daping Hospital, Third Military Medical University, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Weng
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Xiang
authors.initials: X
authors.lastname: Chu
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wu
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Tian
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.forename: Qing
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000150:complications*; D006427:Hemin / Q000494:pharmacology*; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000502:physiology*; D010766:Phosphorylation; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D006427:Hemin; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016194:Receptors, N-Methyl-D-Aspartate; C492716:Nlrp3 protein, mouse