HYPOXIC PRECONDITIONING AND HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE IMMATURE RAT - PATHOLOGICAL AND METABOLIC CORRELATES

It has been reported that immature rats subjected to cerebral hypoxia- ischemia sustain less brain damage if they are previously exposed to s ystemic hypoxia compared with animals not exposed to prior hypoxia. Ac cordingly, neuropathologic and metabolic experiments were conducted to confirm and extend the observation that hypoxic preconditioning prote cts the perinatal brain from subsequent hypoxic-ischemic brain damage, Six-day postnatal rats were subjected to systemic hypoxia with 8% oxy gen at 37 degrees C for 2.5 h. Twenty-four hours later, they were expo sed to unilateral cerebral hypoxia-ischemia for 2.5 h, produced by uni lateral common carotid artery ligation and systemic hypoxia with 8% ox ygen. Neuropathologic analysis, conducted at 30 days of postnatal age, indicated a substantial reduction in the severity of brain damage in the preconditioned rats, such that only 6 of 14 such animals exhibited cystic infarction, but all 13 animals without prior preconditioning e xhibited infarction (p < 0.001). Measurement of cerebral glycolytic an d tricarboxylic acid intermediates and high-energy phosphate reserves at the terminus of and at 4 and 24 h following hypoxia-ischemia showed no differences in the extent of alterations in the preconditioned and nonpreconditioned immature rats. A difference was seen in the restitu tion of high-energy stores during the first 24 h of recovery from hypo xia-ischemia, with a more optimal preservation of these metabolites in the preconditioned animals, reflecting the less severe ultimate brain damage, Accordingly, the neuroprotection afforded to the precondition ed animals was not the result of any differences in the extent of anae robic glycolysis, tissue acidosis, or depletion in high-energy reserve s during hypoxia-ischemia but rather the result of other mechanisms th at improved the metabolic status of the immature brain during the earl y hours of reperfusion following hypoxia-ischemia.