CEREBRAL GLUCOSE AND ENERGY-UTILIZATION DURING THE EVOLUTION OF HYPOXIC-ISCHEMIC BRAIN-DAMAGE IN THE IMMATURE RAT

The cerebral metabolic rate for glucose (CMR(g1)) and cerebral energy utilization (CEU) were assessed in immature rats during recovery from cerebral hypoxia-ischemia. CMR(g1) was determined using a modification of the Sokoloff technique with 2-deoxy-[C-14]glucose (2-DG) as the radioactive tracer. CEU was determined using the Lowry decapitation technique. Seven-day postnatal rats underwent unilateral common carotid artery ligation, followed 4 h thereafter by exposure to 8% oxygen at 37 degrees C for 3 h. At 1, 4, or 24 h of recovery, the rat pups underwent those procedures necessary for the measurement of either CMR(g1) or CEU. At 1 h of recovery, the CMR(1g) of the cerebral hemisphere ipsilateral to the carotid artery occlusion was 97% of the control rate (8.7 mu mol 100 g(-1) min(-1)) but was only 48% of the control in the contralateral hemisphere. At 4 h of recovery, the CMR(g1) was increased 49% above baseline in the ipsilateral hemisphere, decreasing thereafter to 84% of the control at 24 h. The CMR(g1) of the contralateral hemisphere normalized by 4 h of recovery. An inverse correlation between endogenous concentrations of ATP or phosphocreatine and CMR(1g) in the ipsilateral hemisphere was apparent at 4 h of recovery. CEU in the ipsilateral cerebral hemisphere was 64 and 46% of the control (3.47 mmol similar to P/kg/min) at I and 24 h, respectively (p < 0.05) and 77% of the control at 4 h of recovery. CEU in the contralateral hemisphere was unchanged from the control at all measured intervals. Correlation of the alterations in CMR(1g) with those in CEU at the same intervals indicated that substrate supply exceeds energy utilization during early recovery from hypoxia-ischemia. The discrepancy combined with a persistent disruption of the cerebral energy state implies the existence of an uncoupling of mitochondrial oxidative phosphorylation as one mechanism for the occurrence of perinatal hypoxic ischemic brain damage.