Effect of indomethacin on edema following single and repetitive cerebral ischemia in the gerbil

Abstract

Background and Purpose: Repetitive periods of cerebral ischemia result in more severe injury than a single period of ischemia of similar total duration. We investigated the possibility of prostaglandin mediation of this increased injury by attempting to modify brain edema formation with indomethacin pretreatment Methods: Under halothane/N2O anesthesia, groups of gerbils underwent bilateral carotid occlusion to induce forebrain ischemia. Group I underwent a single 15-minute period of carotid occlusion. Group II underwent three 5-minute periods of occlusion at hourly intervals. Groups III and IV were similar to groups I and II, respectively, but received 0.2 mg/kg indomethacin before carotid occlusion. Cortical and ccrebellar water and sodium contents were determined in control animals (n=6) at time zero and in experimental animals 24, 48, and 72 hours after ischemia (n=6-10 gerbils/group at each time point). Results: Cortical water and sodium contents in group II peaked 48 hours after insult (82.15±0.31% and 420 ±14 meq/kg dry wt, respectively) and were significantly higher than control and group I values at both 24 and 48 hours. Cortical water did not change from control in group I animals. Indomethacin pretreatment significantly attenuated increases in water and sodium content seen at 48 hours in gerbils undergoing repetitive ischemia (peak 80.02±0.45% and 300±39 meq/kg dry wt), but did not affect. Conclusions: Indomethacin lessens edema after repetitive cerebral ischemia, suggesting that elevations of cyclooxygenase products are responsible, at least in part, for severe brain edema following repetitive ischemia. © 1991 American Heart Association, Inc.