THE EFFECT OF BOLUS METHYLPREDNISOLONE IN PREVENTION OF BRAIN EDEMA IN HYPOXIC ISCHEMIC BRAIN INJURY - AN EXPERIMENTAL-STUDY IN 7-DAY-OLD RAT PUPS

One of the major mechanisms responsible for tissue injury in hypoxic ischemic brain damage is the formation of free radicals. We studied the efficacy of methylprednisolone, which is claimed to cause rapid congealing of membranes, and to protect the cells against the free radicals present in the environment, in preventing the brain edema that occurs in hypoxic ischemic brain injury. Hypoxic ischemic brain injury to the right hemisphere in 7-day-old rat pups is produced by cauterization of the right common carotid artery followed by hypoxia in 8% oxygen and 92% nitrogen for 3 h. The animals were divided into the groups. One group received methylprednisolone at 30 mg/kg body weight and the other an equal volume of saline 40 min before hypoxia. At 42 h of recovery, some of the rats were killed for measurement of water content in the right and left hemispheres whereas others were killed at 40 days for neuropathological examination. The water content in the right hemisphere was significantly lower in the 19 methylprednisolone-treated pups than it was in 20 saline-treated pups, mean +/- S.E.M. was 83.913 +/- 0.313% and 86.681 +/- 0.377%, respectively. The differences between the means were significant (P < 0.001) according to the Mann-Whitney U-test. The difference of the mean water contents between the two hemispheres was significantly higher in the saline-treated group (2.695 +/- 0.372%) than it was in the methylprednisolone-treated group (0.432 +/- 0.088%), P < 0.0001 by independent samples t-test. Neuropathological study was performed on 4 rat pups. Two of them received methylprednisolone and two of them saline prior to the initiation of the hypoxic insult as described. Histopathologically, changes in the right hemispheres of the saline group that were attributable to the late effects of hypoxia were either absent or present to a minor degree in the methylprednisolone group. Our study suggests that trial of methylprednisolone might be effective if it is given to the mother at risk for fetal hypoxia during labor or to the hypoxic infant right after delivery in preventing hypoxic brain damage.