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 mm(3), 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 1 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.
Shimizu
Katsuyoshi
K
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1083, USA. katsuyoshis@aol.com
Rajapakse
Nishadi
N
Horiguchi
Takashi
T
Payne
R Mark
RM
Busija
David W
DW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology* / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D016166:Free Radical Scavengers; C426066:M40401; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D013482:Superoxide Dismutase