NMDA and Non‐NMDA Receptor Gene Expression Following Global Brain Ischemia in Rats: Effect of NMDA and Non‐NMDA Receptor Antagonists

Domenico E. Pellegrini‐Giampietro, William A. Pulsinelli, R. Suzanne Zukin

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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

Original languageEnglish (US)
Pages (from-to)1067-1073
Number of pages7
JournalJournal of Neurochemistry
Volume62
Issue number3
DOIs
Publication statusPublished - Mar 1994

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Keywords

  • 2,3‐Dihydroxy‐6‐nitro‐7‐sulfamoylbenzo(f)quinoxaline
  • Cerebral ischemia
  • Gene expression
  • NMDA receptor
  • permeability
  • αAmino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor‐Ca

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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