Ischemic neocortical protection with U74006F--a dose-response curve.

A dose-response curve for the lipid peroxidation inhibitor U74006F was established in a rat forebrain ischemia model. Transient forebrain ischemia was induced by bilateral carotid occlusion plus controlled hypotension (50 mmHg) for 10 min. U74006F was administered at doses of 0.3, 1, 3, 7, or 10 mg/kg 30 min prior to ischemia. Control animals received vehicle (0.02 M citrate buffer in 0.8% NaCl). Brains were perfusion-fixed on day 7 post-ischemia for histopathological examination. For both the hippocampus and striatum, neuronal injury was not significantly different between groups. Within the neocortex ischemic neuronal injury was significantly less (P < 0.05) in the 7 mg/kg U74006F-treated group compared to the control, 1 mg/kg, or 3 mg/kg U74006F-treated groups.