Hypoxic-ischemic tolerance phenomenon observed in neonatal rat brain

OBJECTIVE: Our purpose was to determine whether hypoxic-ischemic brain damage would be protected against by advance conditioning of the animal with 4 hours of hypoxic exposure. STUDY DESIGN: Neonatal rats were exposed on postnatal day 7 to (1) 4 hours of hypoxia with 8% oxygen (preconditioning hypoxic group) or (2)4 hours of normoxia (sham-preconditioning group). At 24 hours after the conditioning, rats from both groups were exposed to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen/92% nitrogen). All the rats were killed 1 week after hypoxia-ischemia, and their brains were extracted for histologic study. RESULTS: Two types of brain damage were histologically observed at 1 week after hypoxia-ischemia in both groups: (1) generalized infarction in the ligated hemisphere and (2) predominant neuronal loss in the hippocampal region. The total incidence of brain damage was significantly decreased in the preconditioning hypoxic group (10/24 rats, 41.7%) compared with the sham-preconditioning hypoxic group (17/22 rats, 77.3%; P<.05). CONCLUSION: Our results show that the hypoxic-ischemic tolerance phenomenon may be induced in the hypoxic-ischemic brain damage model by conditioning the animal before the insult with 4 hours of hypoxic exposure.