Protection against ischemic hippocampal CA1 damage in the rat with a new non-NMDA antagonist, NBQX.
Two glutamate antagonists were tested in a rat model of complete, transient cerebral ischemia. Six days after 10 min ischemia the mean loss of hippocampal CA1 pyramidal neurones was 73%. Administration of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) antagonist NBQX (2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline) reduced the pyramidal neurone loss to 1%, 11% and 15%, when given before, immediately after or 1 h after ischemia, respectively. MK-801 (dizocilpine), a competitive NMDA antagonist gave no protection in this model. We suggest that the AMPA receptor transduction mechanisms are sensitized by ischemia and that the postischemic blockade of the main glutamatergic input to the CA1 cells with NBQX impairs the deleterious effect of "normal" postischemic excitatory transmission.
Diemer
N H
NH
Cerebral Ischemia Research Group, University of Copenhagen, Denmark.
Jørgensen
M B
MB
Johansen
F F
FF
Sheardown
M
M
Honoré
T
T
D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002452:Cell Count; D006624:Hippocampus / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology
D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline