Treatment with tamoxifen reduces hypoxic–ischemic brain injury in neonatal rats

Abstract

Tamoxifen, an estrogen receptor modulator, is neuroprotective in adult rats. Does tamoxifen reduce brain injury in the rat pup? Seven-day-old rat pups had the right carotid artery permanently ligated followed by 2.5 h of hypoxia (8% oxygen). Tamoxifen (10 mg/kg) or vehicle was given i.p. 5 min prior to hypoxia, or 5 min after reoxygenation, with a second dose given 6 h after the first. Brain damage was evaluated by weight deficit of the right hemisphere 22 days following hypoxia and gross and microscopic morphology. Tamoxifen pre-treatment reduced brain weight loss from 21.5±4.0% in vehicle pups ( n=27) to 2.6±2.5% in the treated pups ( n=22, P<0.05). Treatment 5 min after reoxygenation reduced brain weight loss from 27.5±4.0% in vehicle pups ( n=42) to 12.0±3.9% in the treated pups ( n=30, P<0.05). Tamoxifen reduces brain injury in the neonatal rat.