Neuroprotective effects of a novel broad-specrtrum cation channel blocker,LOE 908 MS, an experimental focal ischemia: A multispectral study

Thirty-four rats undergoing 90 minutes of temporary middle cerebral artery occlusion were randomly and blindly assigned to vehicle or (RS)-(3, 4-dihyd ro-6,7-dimethoxyisoquinoline-1-gamma 1)-2-phenyl-N,N-di-2-(2,3,4-trimethoxy phenyl)ethyl acetamide (LOE 908 MS; 0.5 mg/kg) i.v, bolus at 30 minutes aft er arterial occlusion followed by a 5 mg/kg/hr i.v. infusion for 3.8 hours (n = 17/group). Perfusion-, diffusion- and T-2-weighted magnetic resonance imaging was performed before treatment and repeatedly after treatment, Mult ispectral analysis was used to define ischemic abnormalities. The size of t he ischemic abnormalities. including the ischemic core and penumbra, was no t different between the two groups before treatment, However, a significant difference in ischemic lesion size was detected beginning 1.5 hours after treatment. The size of the ischemic core was significantly smaller in the t reatment group, while the size of the ischemic penumbra was similar in the two groups at 85 minutes after arterial occlusion, Postmortem infarct size at 24 hours was significantly smaller in the drug-treated group than in the placebo group, These results demonstrate that LOE 908 MS can reduce ischem ic lesion size, which Is probably attributable to inhibition of expansion o f the ischemic core, (C) 1999 Wiley-Liss, Inc.