Influence of Mild Hypothermia on Hypoxic-Ischemic Brain Damage in the Immature Rat

Abstract

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 ipsilateral 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.