GLOBAL CEREBRAL-ISCHEMIA AND REPERFUSION ALTERS NMDA RECEPTOR-BINDINGIN CANINE BRAIN

We employed a canine model to test whether binding to the N-methyl-D-a spartate (NMDA) class of glutamate receptor channels is altered by glo bal cerebral ischemia and/or reperfusion. Ischemia was induced by 10-m in cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. In vitro autoradiography was pe rformed on frozen brain sections with three radioligands: [H-3]glutama te (under conditions to label the NMDA site), [H-3]glycine, and [H-3]M K-801. Modest decreases in [H-3]glutamate and [H-3]MK-801 binding were seen in several regions of hippocampus, and parietal and temporal cor tex at early times after reperfusion, with values returning toward con trol by 24 h. In the striatum, a different pattern was seen: [H-3]glut amate and [H-3]MK-801 binding increased 50-200% at 0.5-4 h after the s tart of reperfusion, returning toward control levels by 24 h. These in creases correlate with findings of increased sensitivity to NMDA-stimu lated release of dopamine from striatal tissue in the same model (Werl ing et al., 1993), and suggest that changes in tissue receptors may co ntribute to the selective vulnerability to ischemic damage during the first hours following reperfusion.