PARADOXICAL MITOCHONDRIAL OXIDATION IN PERINATAL HYPOXIC-ISCHEMIC BRAIN-DAMAGE

Measurements of cytoplasmic and mitochondrial markers of the oxidation -reduction (redox) state of brain tissue were conducted in a perinatal animal model of cerebral hypoxia-ischemia to ascertain underlying bio chemical mechanisms whereby ischemia (reduced oxygen and substrate sup ply) causes brain damage. Seven-day postnatal rats underwent unilatera l common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 h. During the course of hypoxia-ischemia, the rat p ups were quick frozen in liquid nitrogen and their brains processed fo r the enzymatic, fluorometric measurement of cerebral metabolites nece ssary for the calculation of intracellular pH and cytoplasmic and mito chondrial redox states. The results showed an early mitochondrial redu ction followed by re-oxidation during the course of hypoxia-ischemia. The oxidation reflected a partial depletion in accumulated reducing eq uivalents and coincides temporally with the duration of hypoxia-ischem ia required to convert selective neuronal necrosis into cerebral infar ction. The findings suggest that perinatal cerebral hypoxia-ischemia i s characterized more by a limitation of substrate than of oxygen suppl y to the brain, which may explain why glucose supplementation of the i mmature animal improves neuropathologic outcome, in contrast to adults .