Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats

Abstract

To study the efficacy of methylprednisolone/vitamin E in reducing cerebral edema and improving the ultimate neuropathological outcome in perinatal cerebral hypoxia-ischemia, 40 seven-day postnatal rats were subjected to right common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 h. The animals were divided into groups. Twenty rat pups received an intraperitoneal injection of 30 mg/kg body weight methylprednisolone and vitamin E (100 U/kg) immediately following cerebral hypoxia-ischemia. Control animals received either no therapy (n = 10) or an equivalent volume of normal saline (n = 10). After 72 h of recovery from hypoxia-ischemia, the animals were killed and their brains were examined to measure the water contents in the right and left hemispheres (29 rat pups), whereas the others were killed at 21 days for neuropathological examination. Methylprednisolone/vitamin E-treated rats had significantly less water content in the right hemisphere (87.08 +/- 0.28%, mean +/- S.E.M.) than saline-treated animals (89.07 +/- 0.37%, mean +/- S.E.M., P < 0.0001). Methylprednisolone/vitamin E significantly reduced water content in the right hemisphere of the brain. Neuropathological study was performed on nine rat pups. The brains of four methylprednisolone/vitamin E- and five saline-treated pups were examined at the end of the 21-day recovery period. Two groups of the right cerebral cortex included thinning of the cortex. Significantly less damage was seen in the methylprednisolone/vitamin E-treated pups. Our study suggests that trials of methylprednisolone/vitamin E might be effective if they are given to the mother at risk of fetal hypoxia during labor or to the hypoxic infant right after delivery in preventing hypoxic brain damage.