title: Dexmedetomidine attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia reperfusion injury in rats.
abstract: OBJECTIVE
  Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury.
  
  
  METHODS
  Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence.
  
  
  RESULTS
  Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury.
  
  
  CONCLUSIONS
  Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Liaoning, P. R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fang
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Bi
authors.forename: Wen-Fei
authors.initials: WF
authors.lastname: Tan
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D007278:Injections, Spinal; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D042683:Angiopoietin-1; D020927:Dexmedetomidine; D042787:Receptor, TIE-2; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat