NMDA Receptor-dependent increase of cerebral glucose utilization after hypoxia-ischemia in the immature rat.

Post-treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 reduces hypoxic-ischemic brain injury in immature animals. To elucidate possible mechanisms, cerebral glucose utilization (CMRglc) and cerebral blood flow (CBF) were measured 1-5 h after hypoxia-ischemia and administration of MK-801 in 7-day-old rats. After 100 min of unilateral hypoxia-ischemia, half of the pups were injected with MK-801. CMRglc was assessed by the [14C]deoxyglucose (2-DG) method. The brains were analyzed either by autoradiography or for energy metabolites and chromatographic separation of 2-DG-6-phosphate and 2-DG. CBF was measured by the autoradiographic [14C]iodoantipyrine method. Mean CMRglc in the cerebral cortex was increased ipsilaterally after hypoxia-ischemia to 15 +/- 3.3 mumol 100 g-1 min-1 (p < 0.01) and areas with CMRglc > 20 mumol 100 g-1 min-1 amounted to 8.0 +/- 7.7 mm2 in the ipsilateral hemisphere compared with 1.2 +/- 1.6 mm2 contralaterally (p < 0.001). Treatment with MK-801 decreased CMRglc bilaterally (p < 0.05) and reduced ipsilateral areas with increased CMRglc by 64% (p < 0.01). CBF was unaltered after hypoxia-ischemia and by MK-801 treatment. In conclusion, regional glucose hyperutilization in the parietal cortex after hypoxia-ischemia was attenuated by MK-801; this may have relevance to the neuroprotective effect of NMDA-receptor antagonists in this model.