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


CONCLUSIONS
Ifenprodil given before CA is associated with a downregulation of brain AQP4 in rats.
Xiao
F
F
Department of Emergency Medicine, Louisiana State University Health Science Center, Shreveport 71130, USA. fxiao@lsuhsc.edu
Pardue
S
S
Arnold
T C
TC
Monroe
J
J
Alexander
J S
JS
Carden
D L
DL
Turnage
R
R
Conrad
S A
SA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage
D010880:Piperidines; D014665:Vasodilator Agents; C010739:ifenprodil