Delayed treatment with 5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione, a glycine site N-methyl-D-aspartate antagonist, protects against permanent middle cerebral artery occlusion in male rats

Abstract

The glycine site, N-methyl-D-aspartate antagonist 5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione (ACEA1021) was previously tested only in models of transient stroke with pre-treatment paradigms. We therefore tested whether it would protect in two models of permanent stroke in two rat strains with delayed treatment. Intravenous ACEA1021 reduced cerebral infarction by 62% (15 min treatment delay) and 42% (2 h treatment delay), relative to vehicle-injected rats, when subjected to a modified Tamura and permanent intraluminal filament model of stroke, respectively. In comparison, intravenous nicotinamide (500 mg/kg), which was tested in separate animal cohorts, had no significant effect on infarction. These data show that ACEA1021 protects against permanent focal cerebral ischemia, even with a 2 h post-treatment delay. Characterization of the therapeutic window with longer outcome times including infarction and neurobehavioral endpoints is needed.