title: Spinal cord protection via alpha-2 agonist-mediated increase in glial cell-line-derived neurotrophic factor.
abstract: OBJECTIVE
  Delayed paraplegia secondary to ischemia-reperfusion injury is a devastating complication of thoracoabdominal aortic surgery. Alpha-2 agonists have been shown to attenuate ischemia-reperfusion injury, but the mechanism for protection has yet to be elucidated. A growing body of evidence suggests that astrocytes play a critical role in neuroprotection by release of neurotrophins. We hypothesize that alpha-2 agonism with dexmedetomidine increases glial cell-line-derived neurotrophic factor in spinal cord astrocytes to provide spinal cord protection.
  
  
  METHODS
  Spinal cords were isolated en bloc from C57BL/6 mice, and primary spinal cord astrocytes and neurons were selected for and grown separately in culture. Astrocytes were treated with dexmedetomidine, and glial cell-line-derived neurotrophic factor was tested for by enzyme-linked immunosorbent assay. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to assess neuronal viability.
  
  
  RESULTS
  Spinal cord primary astrocytes treated with dexmedetomidine at 1 μmol/L and 10 μmol/L had significantly increased glial cell-line-derived neurotrophic factor production compared with control (P < .05). Neurons subjected to oxygen glucose deprivation had significant preservation (P < .05) of viability with use of dexmedetomidine-treated astrocyte media. Glial cell-line-derived neurotrophic factor neutralizing antibody eliminated the protective effects of the dexmedetomidine-treated astrocyte media (P < .05).
  
  
  CONCLUSIONS
  Astrocytes have been shown to preserve neuronal viability via release of neurotrophic factors. Dexmedetomidine increases glial cell-derived neurotrophic factor from spinal cord astrocytes via the alpha-2 receptor. Treatment with alpha-2 agonist dexmedetomidine may be a clinical tool for use in spinal cord protection in aortic surgery.
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo. Electronic address: kirsten.freeman@ucdenver.edu.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Freeman
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Foley
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Marshall T
authors.initials: MT
authors.lastname: Bell
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cleveland
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Joshua
authors.initials: J
authors.lastname: Mares
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Anesthesiology, University of Colorado Denver, Denver, Colo.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Puskas
authors.affiliation: Department of Surgery, University of Colorado Denver, Denver, Colo.
authors.forename: T Brett
authors.initials: TB
authors.lastname: Reece
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D018929:Cell Culture Techniques; D020927:Dexmedetomidine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000150:complications*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D020760:Spinal Cord Ischemia / Q000209:etiology* / Q000517:prevention & control*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D020927:Dexmedetomidine