title: Cold-inducible RNA-binding protein mediates neuroinflammation in cerebral ischemia.
abstract: BACKGROUND
  Neuroinflammation is a key cascade after cerebral ischemia. Excessive production of proinflammatory mediators in ischemia exacerbates brain injury. Cold-inducible RNA-binding protein (CIRP) is a newly discovered proinflammatory mediator that can be released into the circulation during hemorrhage or septic shock. Here, we examine the involvement of CIRP in brain injury during ischemic stroke.
  
  
  METHODS
  Stroke was induced by middle cerebral artery occlusion (MCAO). In vitro hypoxia was conducted in a hypoxia chamber containing 1% oxygen. CIRP and tumor necrosis factor-α (TNF-α) levels were assessed by RT-PCR and Western blot analysis.
  
  
  RESULTS
  CIRP is elevated along with an upregulation of TNF-α expression in mouse brain after MCAO. In CIRP-deficient mice, the brain infarct volume, induction of TNF-α, and activation of microglia are markedly reduced after MCAO. Using microglial BV2 cells, we demonstrate that hypoxia induces the expression, translocation, and release of CIRP, which is associated with an increase of TNF-α levels. Addition of recombinant murine (rm) CIRP directly induces TNF-α release from BV2 cells and such induction is inhibited by neutralizing antisera to CIRP. Moreover, rmCIRP activates the NF-κB signaling pathway in BV2 cells. The conditioned medium from BV2 cells exposed to hypoxia triggers the apoptotic cascade by increasing caspase activity and decreasing Bcl-2 expression in neural SH-SY5Y cells, which is inhibited by antisera to CIRP.
  
  
  CONCLUSIONS
  Extracellular CIRP is a detrimental factor in stimulating inflammation to cause neuronal damage in cerebral ischemia.
  
  
  CONCLUSIONS
  Development of an anti-CIRP therapy may benefit patients with brain ischemia.
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA; Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA. Electronic address: mzhou@nshs.edu.
authors.forename: Mian
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA; Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA. Electronic address: wlyang@nshs.edu.
authors.forename: Weng-Lang
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA; Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA. Electronic address: kevinji78@gmail.com.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA; Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA. Electronic address: xqiang@nshs.edu.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Qiang
authors.affiliation: Center for Translational Research, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA; Hofstra North Shore-LIJ School of Medicine, Manhasset, NY 11030, USA. Electronic address: pwang@nshs.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020521:Stroke / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C106176:Cirbp protein, mouse; D016328:NF-kappa B; D016601:RNA-Binding Proteins; D014409:Tumor Necrosis Factor-alpha
keywords: Cerebral ischemia; Cold shock protein; Hypoxia; Inflammation; Microglia; Neural cell