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.
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.
Sarhan
Shakir
S
CNS Disease Group, Aventis Inc., 1041 Route 202-206, Bridgewater, NJ 08807, USA.
Wettstein
Joseph G
JG
Maynard
Kenneth I
KI
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000517:prevention & control*; D007275:Injections, Intravenous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013997:Time Factors
D018696:Neuroprotective Agents; D011810:Quinoxalines; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C092062:licostinel