Broad-spectrum cation channel inhibition by LOE 908 MS reduces infarct volume in vivo and postmortem in focal cerebral ischemia in the rat

Cation channels conduct calcium, sodium and potassium, cations that are lik ely deleterious in the evolution of focal ischemic injury. We studied the e ffects of a novel, broad-spectrum inhibitor of several cation channels, LOE 908 MS, on acute ischemic lesion development with diffusion-weighted magne tic resonance imaging (DWI) and on cerebral perfusion with perfusion imagin g (PI) in vivo and on cerebral infarct size using 2,3,5-triphenyltetrazoliu m chloride (TTC) staining postmortem. A total of 18 male Sprague-Dawley rat s underwent 90 min of middle cerebral artery occlusion (MCAO) and were rand omly and blindly assigned to either LOE 908 MS or vehicle starting 30 min a fter inducing focal ischemia and continuing for 4 h. Whole-brain DWI and mu ltislice PI were done before initiation of treatment and repeated frequentl y for the next 3,5 h. DWI-derived lesion volume at 4 h showed a significant difference in favor of the drug treated group (P=0.03), whereas PI-derived perfusion deficit volumes did not significantly differ between the groups. The postmortem infarct volume at 24 h was significantly attenuated in the treated group in comparison to controls (P=0.0001) and neurological score w as significantly better in the treated group (P<0.02). Blocking several dis tinct cation channels with LOE 908 MS significantly reduced infarct size an d improved neurological outcome without observable adverse effects in this focal ischemia model. (C) 2000 Elsevier Science B.V. All rights reserved.