NEUROPROTECTION FROM ISCHEMIC BRAIN INJURY BY HYPOXIC PRECONDITIONINGIN THE NEONATAL RAT

Very recent studies in adult gerbils and rats have shown that exposure to sublethal ischemia can confer neuroprotection from subsequent leth al ischemic episodes. To determine if a similar phenomenon can be elic ited during the perinatal period, we have developed a preconditioning regimen that involves exposure to normothermic hypoxia (8% oxygen) 24 h prior to hypoxia-ischemia in the well-established post-natal-day 7 r at pup model [20]. Significant infarction, manifested as a 34 +/- 4% r eduction in cerebral hemispheric weight ipsilateral to the carotid lig ation, was noted in control animals (n = 24) one week after hypoxia-is chemia, whereas littermates preconditioned with 3 h hypoxia (n = 29) s howed no evidence of hemispheric necrosis. Lack of injury in the latte r animals was confirmed at the cellular level by histopathologic analy ses of Nissl-stained coronal sections. Thus, pre-exposure to hypoxia i nduces endogenous adaptive mechanisms that can protect the perinatal b rain from hypoxic-ischemic injury.