Blockade of the AMPA receptor prevents CA1 hippocampal injury following severe but transient forebrain ischemia in adult rats.
The cytoprotective effect of NBQX, a selective AMPA receptor antagonist, was tested following 10 min of severe forebrain ischemia using the 4-vessel occlusion model. Immediately, and at 15 and 30 min following reperfusion, adult Wistar rats received intraperitoneal injections of either saline (n = 5), 1 mg lithium chloride (n = 17) or 30 mg/kg of the lithium salt of NBQX (n = 18). In saline-treated animals 82 +/- 12% of CA1 hippocampal neurons were lost. Of those treated with lithium 70 +/- 23% were injured, while those given NBQX sustained only 40 +/- 34% CA1 necrosis (P less than 0.01). Twelve of 18 NBQX-treated animals had less than 30% CA1 injury as compared with 1 of 17 lithium-treated animals. The AMPA receptor may play a more important role than the NMDA receptor in selective ischemic necrosis of hippocampal neurons.
Buchan
A M
AM
Division of Neurology and Neuroscience, Ottawa Civic Hospital, University of Ottawa, Canada.
Li
H
H
Cho
S
S
Pulsinelli
W A
WA
D000818:Animals; D016923:Cell Death; D002712:Chlorides / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D009474:Neurons / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D015424:Reperfusion; D012965:Sodium Chloride / Q000494:pharmacology
D002712:Chlorides; D011810:Quinoxalines; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D012965:Sodium Chloride; D008094:Lithium; D018021:Lithium Chloride