The effects of indomethacin on neuronal apoptosis in newborn rats with hypoxic-ischemic brain injury

Purpose: Cyclooxygenase pathway and prostaglandins plays an important role in the pathogenesis and delayed mechanisms of hypoxic-ischemic brain injury. The aim of this study was to investigate the effect of different doses of indomethacin, a nonselective cyclooxygenase inhibitor, on neuronal apoptosis in rats with hypoxic-ischemic brain injury.Material and Methods: Seven-day-old rat pups with the Rice model of hypoxic-ischemic cerebral injury were randomly divided into five groups. Group I (n: 15) pups were given physiologic saline, but neither ligation nor hypoxia were performed. Group II (n: 15) pups were treated with physiologic saline after hypoxic-ischemia. Group III (n: 15) pups were treated with indomethacin at a dose of 2 mg/kg per before hypoxic ischemia. Group IV (n: 15) pups were treated with three doses of indomethacin at a dose of 2 mg/kg every 12 h after hypoxic-ischemia. Group V (n: 15) pups were treated with three doses of indomethacin, at a dose of 4 mg/kg every 12 h after hypoxic ischemia. After 72 hours, the rats were decapitated and each brain hemispheres tissues were evaluated by using the TUNEL staining method.Results: Indomethacin treatment either before or after hypoxia, results in a significant reduction in the numbers of apoptotic cells in rat brains when it is compared with group treated with physiologic saline after hypoxic-ischemia (p<0,001).Conclusion: These results demonstrated that indomethacin administration either before or after hypoxic-ischemia reduce neuronal apoptosis, and we propose that indomethacin may be a good option for the therapy of hypoxic-ischemic brain injury.Key Words: Hypoxic ischemia, brain injury, apoptosis, indomethacin