Protective effect of a new nonpeptidyl mimetic of SOD, M40401, against focal cerebral ischemia in the rat

We tested the neuroprotective effects of M40401, a new, low molecular weight (511.4 Da) maganese superoxide dismutase mimetic, against 90 min of middle cerebral artery occlusion (MCAO) in male Wistar rats. Animals received a single injection of vehicle (n=8), 1 mg/kg (n=6), or 3 mg/kg (n=7) 30 min before MCAO. Total lesion volume was reduced only in the group receiving 3 mg/kg M40401 (163.5 +/- 18.7 versus 43.4 +/- 7.0 Min, for vehicle and M40401, respectively; P<0.05), with almost complete reduction of lesion volume in the cortex but little protection in the basal ganglia. Neurological score was also improved in this group. The dose of I mg/kg M40401 had smaller and inconsistent effects on lesion parameters. Administration of a single dose of 3 mg/kg M40401 at 60 min of MCAO or at the end of MCAO (90 min) failed to significantly reduce lesion volume. A single dose of M40401 plus prolonged infusion into the post-MCAO period also failed to decrease lesion volume significantly. These data indicate that M40401 protects cerebral tissue from ischemic insult when administered before MCAO, probably by limiting damage mediated by detrimental actions of superoxide anion. (C) 2002 Elsevier Science B.V. All rights reserved.