NMDA and Non-NMDA Receptor Gene Expression Following Global Brain Ischemia in Rats: Effect of NMDA and Non-NMDA Receptor Antagonists |
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Authors: | Domenico E Pellegrini-Giampietro William A Pulsinelli R Suzanne Zukin |
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Institution: | Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York;Cerebrovascular Diseuse Reseurch Center, Department of Neurology and Neuroscience, Cornell University Medical Center, Nclw York, New York, U.S.A. |
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Abstract: | Abstract: Transient forebrain or global ischemia in rats induces selective and delayed damage of hippocampal CA1 neurons. In a previous sludy, we have shown that expression of GIuR2, the kainate/a-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA) receptor subunit that governs Ca' permeability, is preferentially reduced in CA1 at a time point proceeding neuronal degeneration. Postischemic administration of the selective AMPA receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), protects CAI neurons against delayed death. In this study we examined the effects of NBQX (at a neuroprotective dose) and of MK-801 (a selective NMDA receptor anltagonist, not protective in this model) on kainate/AMPA receptor gene expression changes after global ischemia. We also examined the effects of transient forebrain ischemia on expression of the NMDA receptor subunit NMDARI. In ischemic rats treated with saline, GIuR2 and (31uR3 mRNAs were markedly reduced in CAI but were unchanged in CA3 or dentate gyrus. GluRl and NMDAR1 mRNAs were not significantly changed in any region examined. Administration of NBQX or MK-801 did not alter the ischemia-induced changes in kainate/AMPA receptor gene expression. These findings suggest that NBQX affords neuroprotection by a direct blockade of kainate/AMPA receptors, rather than by a modificatian of GIuR2 expression changes |
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Keywords: | αAmino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-Ca2 permeability Cerebral ischemia Gene expression 2 3-Dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline NMDA receptor |
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