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.
Gilland
E
E
Department of Obstetrics and Gynecology, University of Göteborg, Sweden.
Hagberg
H
H
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D003847:Deoxyglucose / Q000097:blood / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D005958:Glucosephosphates; D016194:Receptors, N-Methyl-D-Aspartate; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D016291:Dizocilpine Maleate; D003847:Deoxyglucose; D005947:Glucose