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

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 cerebellar 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 mortality. 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.