The AMPA antagonist NBQX protects thalamic reticular neurons from degeneration following cardiac arrest in rats.
Thalamic reticular (RT) neurons are selectively vulnerable to degeneration following global ischemia. The degenerative mechanism is thought to involve an excitotoxic component, mediated in part by sustained post-ischemic activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) type excitatory amino acid (EAA) receptors. In order to test this hypothesis, the selective competitive AMPA type EAA antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F) quinoxalinedione) was administered at 30 mg/kg to rats 1, 3, and 6 h after resuscitation from 10 min cardiac arrest. NBQX treatment resulted in a 2-fold increase of spared RT neurons, from a mean density of 3.6 +/- 0.8 x 10(3) neurons/mm3 in cardiac arrest cases to 7.4 +/- 1.1 x 10(3) neurons/mm3 in the NBQX treated group, which represents sparing of 41.7% of the normal population of RT neurons, and protection of 26.9% of vulnerable RT neurons. Neurons within the central core of the RT manifest both a higher degree of vulnerability to ischemic degeneration, > 92% loss, and a higher sensitivity to sparing following NBQX administration, 460% increased sparing, than neuronal sub-populations in the medial or lateral 1/3 of the RT. Protection by post-arrest administration of NBQX suggests that sustained post-arrest stimulation of AMPA receptors is an important component in the process of ischemic degeneration of RT neurons.
Ross
D T
DT
Head Injury Center, University of Pennsylvania, Philadelphia 19104-4283, USA.
Brasko
J
J
Patrikios
P
P
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006323:Heart Arrest / Q000503:physiopathology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D012154:Reticular Formation / Q000166:cytology* / Q000187:drug effects; D013788:Thalamus / Q000166:cytology* / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline