Global cerebral ischemia and reperfusion alters NMDA receptor binding in canine brain.
We employed a canine model to test whether binding to the N-methyl-D-aspartate (NMDA) class of glutamate receptor channels is altered by global cerebral ischemia and/or reperfusion. Ischemia was induced by 10-min cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. In vitro autoradiography was performed on frozen brain sections with three radioligands: [3H]glutamate (under conditions to label the NMDA site), [3H]glycine, and [3H]MK-801. Modest decreases in [3H]glutamate and [3H]MK-801 binding were seen in several regions of hippocampus, and parietal and temporal cortex at early times after reperfusion, with values returning toward control by 24 h. In the striatum, a different pattern was seen: [3H]glutamate and [3H]MK-801 binding increased 50-200% at 0.5-4 h after the start of reperfusion, returning toward control levels by 24 h. These increases correlate with findings of increased sensitivity to NMDA-stimulated release of dopamine from striatal tissue in the same model (Werling et al., 1993), and suggest that changes in tissue receptors may contribute to the selective vulnerability to ischemic damage during the first hours following reperfusion.
Wei
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Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037, USA.
Fiskum
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Rosenthal
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Perry
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DC
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004285:Dogs; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006323:Heart Arrest; D006624:Hippocampus / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009928:Organ Specificity; D010296:Parietal Lobe / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015424:Reperfusion; D013702:Temporal Lobe; D013997:Time Factors; D014316:Tritium
D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D005998:Glycine