TY - JOUR
T1 - Protective effect of a new nonpeptidyl mimetic of SOD, M40401, against focal cerebral ischemia in the rat
AU - Shimizu, Katsuyoshi
AU - Rajapakse, Nishadi
AU - Horiguchi, Takashi
AU - Payne, R. Mark
AU - Busija, David W.
N1 - Funding Information:
This research was supported by National Heart, Lung, and Blood Institute Grants HL-30260, HL-46558, HL-50587, AHA Mid Atlantic affiliate Grant 9951272U, AHA Bugher Foundation Award 0270114N, and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-55765. M40401 was a generous gift from MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St. Louis, MO 63114, USA. We thank Dr. Daniela Salvemini for her helpful critique of the manuscript.
PY - 2003/2/14
Y1 - 2003/2/14
N2 - 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 mm3, 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.
AB - 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 mm3, 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.
KW - Cerebral ischemia
KW - Middle cerebral artery occlusion
KW - Superoxide anion
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U2 - 10.1016/S0006-8993(02)03796-4
DO - 10.1016/S0006-8993(02)03796-4
M3 - Article
C2 - 12560107
AN - SCOPUS:0037435874
SN - 0006-8993
VL - 963
SP - 8
EP - 14
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -