title: The AMPA antagonist NBQX protects thalamic reticular neurons from degeneration following cardiac arrest in rats.
abstract: 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.
authors.affiliation: Head Injury Center, University of Pennsylvania, Philadelphia 19104-4283, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Ross
authors.forename: J
authors.initials: J
authors.lastname: Brasko
authors.forename: P
authors.initials: P
authors.lastname: Patrikios
mesh_terms: 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
chemical_list: D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline