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 language | English (US) |
|---|---|
| Pages (from-to) | 764-771 |
| Number of pages | 8 |
| Journal | Anesthesiology |
| Volume | 77 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1992 |
| Externally published | Yes |
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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
Cite this
AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia. / Matsumoto, M.; Zornow, Mark; Scheller, M. S.; Strnat, M. A P.
In: Anesthesiology, Vol. 77, No. 4, 1992, p. 764-771.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia
AU - Matsumoto, M.
AU - Zornow, Mark
AU - Scheller, M. S.
AU - Strnat, M. A P
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Animals: rabbit
KW - Antagonists, AMPA receptor: NBQX
KW - Antagonists, NMDA receptor: MK801
KW - Brain
KW - Brain: ischemia
KW - Excitatory amino acids: aspartate; glutamate
KW - Measurement techniques: microdialysis
KW - Receptors: AMPA; NMDA
UR - http://www.scopus.com/inward/record.url?scp=0026655574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026655574&partnerID=8YFLogxK
U2 - 10.1097/00000542-199210000-00022
DO - 10.1097/00000542-199210000-00022
M3 - Article
VL - 77
SP - 764
EP - 771
JO - Anesthesiology
JF - Anesthesiology
SN - 0003-3022
IS - 4
ER -