AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia

M. Matsumoto, M. H. Zornow, M. S. Scheller, M. A.P. Strnat

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Increased extracellular concentrations of glutamate during episodes of cerebral ischemia may be due in part to a positive glutaminergic feedback loop. We evaluated the effect of selective AMPA or NMDA receptor antagonists on hippocampal extracellular concentrations of excitatory amino acids during ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10 min of global cerebral ischemia produced by neck tourniquet inflation (20 psi) combined with systemic hypotension during halothane (1-1.5%) anesthesia. Hippocampal extracellular concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5 mg · kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by an infusion of 5 mg · kg-1 · h-1. The MK801 group (n = 5) received 1 mg · kg-1 of MK801 (dissolved in 5% dextrose) over 5 min followed by 580 μg · kg-1 · h-1. The 5% dextrose group (n = 4) received an equivalent volume of 5% dextrose. The peak concentrations of glutamate, aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold, and 4-5-fold higher than preischemic values, respectively. There were no significant differences, however, among the three groups in the concentrations of glutamate, aspartate, or glycine at any time during the study. These results do not support the existence of a positive feedback loop for glutamate mediated via AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or reperfusion.

Original languageEnglish (US)
Pages (from-to)764-771
Number of pages8
JournalAnesthesiology
Volume77
Issue number4
DOIs
StatePublished - Oct 23 1992

Keywords

  • Animals: rabbit
  • Antagonists, AMPA receptor: NBQX
  • Antagonists, NMDA receptor: MK801
  • Brain
  • Brain: ischemia
  • Excitatory amino acids: aspartate; glutamate
  • Measurement techniques: microdialysis
  • Receptors: AMPA; NMDA

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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