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

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. (C) 2003 Elsevier B.V. All rights reserved.