Hypoxic-ischemic tolerance induced by hyperthermic pretreatment in newborn rats

We investigated the effect of hyperthermic pretreatment 24 hours before hypoxic-ischemic exposure on neuronal cell damage in 7-day-old rats.

Newborn rats were separated on postnatal day 7 into two groups: 1) preheated (those exposed to 2 hours of hyperthermic pretreatment at 42-43C) (n = 29), and 2) nonheated (n = 20). At 24 hours after the hyperthermic stress, rats from both groups were subjected to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen/92% nitrogen) at 33C. All rats were killed 1 week after hypoxia-ischemia, and brains were extracted for histologic study. A different group of 7-day-old rats (n = 8) was placed in the same hyperthermic environment as mentioned above for 2 hours, and 24 hours after heat exposure brains were extracted for immunohistochemistry of heat-shock protein 70.

The total incidence of hypoxic-ischemic brain damage significantly decreased in the preheated group (12 of 25 [48%]) compared with the nonheated group (17 of 20 [85%]; P < .03). The induction of immunoreactive heat-shock protein 70 was observed mainly in glial and vascular endothelial cells and, in a lesser amount, in neuronal cells of the cerebral cortex and hippocampus.

Incidence of hypoxic-ischemic brain damage is consistently reduced by 2 hours of hyperthermic pretreatment in 7-day-old rats.