Influence of mild hypothermia on hypoxic-ischemic brain damage in the immature rat

Abstract

Recent studies in adult animals have shown that even small decreases in brain or core temperature ameliorate the damage resulting from hypoxic-ischemic insults. To determine the effect of minor reductions in ambient temperature either during or after an hypoxic-ischemic insult on the brain of the immature rat, 7-d-postnatal rat pups underwent unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 3 h. Control animals were maintained at 37°C during hypoxia-ischemia. Intraischemic hypothermia was induced during the insult at temperatures of 34°C and 31 °C. Postischemic hypothermia was induced by exposing rat pups that underwent hypoxia at 37°C to recovering environments of 34°C and 31°C. Temperatures were recorded every 15 min from thermistor probes placed in the ipsilat-eral hemisphere and rectally. Neuropathologic alterations were assessed at 30 postnatal d. During hypoxia, animals became poikilothermic. Brain damage occurred in 90% of rat pups exposed to hypoxia-ischemia at 37°C. Cerebral injury significantly decreased with decreasing temperatures during hypoxia-ischemia (p < 0.01). Only 30% of rats had brain damage when exposed to hypoxia-ischemia at 34°C, and none of the rats exposed at 31°C had brain damage. In contrast, there was no difference in the extent of cerebral injury between rat pups recovered under hypothermic conditions of either 34°C or 31°C compared with those recovered at 37°C. The results indicate that reductions in temperature of 3 to 6°C have a protective effect during but not immediately after hypoxia-ischemia. These findings have important implications about the thermoregulatory control of the sick newborn infant. © 1993 International Pediatric Research Foundation, Inc.