Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats

Br J Anaesth. 2014 Jul;113(1):168-76. doi: 10.1093/bja/aet352. Epub 2013 Nov 24.

Abstract

Background: This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI.

Methods: Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining.

Results: Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls.

Conclusions: Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion.

Keywords: neuroprotectant; spinal cord, ischaemia–reperfusion injury; xenon, delayed postconditioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carbon Dioxide / blood
  • Drug Administration Schedule
  • Ischemic Postconditioning / methods*
  • Locomotion / drug effects
  • Male
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Oxygen / blood
  • Partial Pressure
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Spinal Cord / blood supply
  • Spinal Cord Ischemia / pathology
  • Spinal Cord Ischemia / physiopathology
  • Spinal Cord Ischemia / prevention & control*
  • Xenon / administration & dosage*
  • Xenon / pharmacology
  • Xenon / therapeutic use

Substances

  • Neuroprotective Agents
  • Carbon Dioxide
  • Xenon
  • Oxygen