Ifenprodil treatment is associated with a down-regulation of brain aquaporin 4 following cardiac arrest in rats

Acta Neurochir Suppl. 2005:95:415-9. doi: 10.1007/3-211-32318-x_85.

Abstract

Objectives: Ifenprodil, a NMDA receptor polyamine site antagonist, reduces experimental cardiac arrest (CA)-elicited brain edema, which is associated with an up-regulation of aquaporin 4 (AQP4), a brain water-selective channel. However, the interacting roles of NMDA receptors and AQP4 in CA-elicited brain edema are unknown. The objective of this study was to test our hypothesis that ifenprodil treatment is associated with a down-regulation of brain AQP4.

Methods: Twenty-five rats were assigned to normal controls (group 1, n = 6) or subjected to eight minutes of asphyxial CA treated with placebo (group 2, n = 9) or ifenprodil (group 3, n = 10). Ifenprodil at 10 mg/kg or normal saline of equal volume was given intraperitoneally, 5 minutes before CA. The density of AQP4 protein and actin bands was scanned and expressed as the ratios of the optical density of AQP4 relative to that of actin. The ANOVA analysis was used to compare the group differences.

Results: The ratios of the optical density of AQP4 to that of actin were 0.88 +/- 0.06 in group 1, 1.11 +/- 0.08 in group 2 (p < 0.05 vs. group 1), and 0.78 +/- 0.04 in group 3 (p < 0.01 vs. group 2; NS vs. group 1).

Conclusion: Ifenprodil given before CA is associated with a downregulation of brain AQP4 in rats.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Edema / drug therapy*
  • Brain Edema / etiology
  • Brain Edema / metabolism*
  • Down-Regulation / drug effects
  • Heart Arrest / complications
  • Heart Arrest / drug therapy*
  • Heart Arrest / metabolism*
  • Phosphorylation / drug effects
  • Piperidines / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage

Substances

  • Piperidines
  • Vasodilator Agents
  • ifenprodil