Estrogen attenuates hypoxic-ischemic brain injury in neonatal rats

Estrogen is neuroprotective in adult animals. We wished to determine if estrogen protects against brain injury in the newborn. Four-day-old rat pups were treated with subcutaneously implanted pellets containing 0.05 mg (2.4 microg/day) of 17beta-estradiol or vehicle, designed to release the estrogen over 21 days. At 7 days old the pups had the right carotid artery ligated followed by 2.5 h of 8% oxygen. Brain damage was evaluated by weight deficit of the right hemisphere at 22 days following hypoxia. Estradiol treatments reduced brain weight loss from -17.4+/-2.8% S.E.M. in the vehicle group (n=32) to -9.3+/-2.7% in the treated group (n=32, P<0.05). Brain cortex thiobarbituric acid reacting substances and caspase activities were assessed 24 h after reoxygenation. Estradiol significantly reduced a hypoxia-induced increase in brain thiobarbituric acid reactive substances (P<0.05). Levels of caspase-3, -8 and -9 activity increased due to hypoxia-ischemia. Estradiol had no effect on caspase activity. Estradiol reduced brain injury in the neonatal rat.