title: Cytosolic phospholipase A2 protein as a novel therapeutic target for spinal cord injury.
abstract: OBJECTIVE
  The objective of this study was to investigate whether cytosolic phospholipase A2 (cPLA2 ), an important isoform of PLA2 that mediates the release of arachidonic acid, plays a role in the pathogenesis of spinal cord injury (SCI).
  
  
  METHODS
  A combination of molecular, histological, immunohistochemical, and behavioral assessments were used to test whether blocking cPLA2 activation pharmacologically or genetically reduced cell death, protected spinal cord tissue, and improved behavioral recovery after a contusive SCI performed at the 10th thoracic level in adult mice.
  
  
  RESULTS
  SCI significantly increased cPLA2 expression and activation. Activated cPLA2 was localized mainly in neurons and oligodendrocytes. Notably, the SCI-induced cPLA2 activation was mediated by the extracellular signal-regulated kinase signaling pathway. In vitro, activation of cPLA2 by ceramide-1-phosphate or A23187 induced spinal neuronal death, which was substantially reversed by arachidonyl trifluoromethyl ketone, a cPLA2 inhibitor. Remarkably, blocking cPLA2 pharmacologically at 30 minutes postinjury or genetically deleting cPLA2 in mice ameliorated motor deficits, and reduced cell loss and tissue damage after SCI.
  
  
  CONCLUSIONS
  cPLA2 may play a key role in the pathogenesis of SCI, at least in the C57BL/6 mouse, and as such could be an attractive therapeutic target for ameliorating secondary tissue damage and promoting recovery of function after SCI.
authors.affiliation: Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Department of Neurological Surgery, and Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Nai-Kui
authors.initials: NK
authors.lastname: Liu
authors.forename: Ling-Xiao
authors.initials: LX
authors.lastname: Deng
authors.forename: Yi Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Qing-Bo
authors.initials: QB
authors.lastname: Lu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Wang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Hu
authors.forename: Eddie
authors.initials: E
authors.lastname: Oakes
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Bonventre
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Shields
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xu
mesh_terms: D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D004789:Enzyme Activation / Q000235:genetics; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D018390:Gene Targeting / Q000379:methods*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009570:Nitriles / Q000008:administration & dosage; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology / Q000473:pathology; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D054513:Group IV Phospholipases A2