A NEW ANTIOXIDANT DRUG LIMITS BRAIN-DAMAGE INDUCED BY TRANSIENT CEREBRAL-ISCHEMIA

Restoration of blood flow after an ischaemic event generates the forma tion of oxygen radicals which could augment brain damage. The authors studied the effects of different doses (50, 100, 200 mg/kg/i.p.) of a new antioxidant, IRFI-016, 2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzof uranyl) acetic acid] on brain damage in the Mongolian gerbil induced b y 5 min of bilateral carotid occlusion (BCO) followed by reperfusion. Post-ischaemic brain malondialdehyde (MDA) levels and locomotor activi ty at different times and delayed neuronal death of hippocampal CA(1) area on the fourth day after occlusion were evaluated. During reperfus ion, after BCO, enhancement of brain MDA occurs (37.5%, 62.5% and 100% at 15, 30 and 60 min of reperfusion, respectively). Brain MDA postisc haemic increases were reduced at 15 min of reperfusion to 15.4% and 44 .4% by IRFI-016, 100 and 200 mg/kg, respectively. After 30 min of repe rfusion brain MDA was reduced to 31.25% and 53.13% by IRIF-016 100 and 200 mg/kg, respectively. Hyperactivity and delayed neuronal death of CA(1) were significantly reduced in postischaemic gerbils treated with the highest doses of IRIF-016. Results indicate that pretreatment wit h the antioxidant IRIF-016 improves in a dose-dependent manner brain d amage induced by ischaemia and reperfusion in the gerbil.