The purpose of the present study was to determine after what time period hydroxyl radical formation contributes most to ischemic brain damage in focal ischemia, using a hydroxyl radical scavenger, EPC-K1, l-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-tridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium salt. Focal ischemia was produced by thrombotic occlusion of the left middle cerebral artery in rats. After evaluation of the pharmacokinetics of EPC-K1in the brain tissue and plasma following 10 mg/kg intravenous bolus treatment of conscious rats, we investigated the neuroprotective effect of EPC-K1in the middle cerebral artery occlusion model. A single intravenous bolus of EPC-K1was given immediately, 3 or 6 h after ischemia, and cerebral brain damage was measured 24 h after ischemia. When EPC-K1was injected 3 h after ischemia, a significant (P<0.01) reduction of cerebral brain damage was observed. EPC-K1delivered by intravenous infusion that started immediately after ischemia and lasted for 24 h, also significantly (P<0.05) reduced brain damage, but the efficacy of the neuroprotective effect was the same as that of the 3 h after ischemia bolus treatment. These results may indicate that the period of hydroxyl radical formation most critical for ischemic brain damage is a few hours after the third hour following ischemia in this model. Copyright (C) 1998 Elsevier Science B.V.
Takamatsu, H., Kondo, K., Ikeda, Y., & Umemura, K. (1998). Hydroxyl radical generation after the third hour following ischemia contributes to brain damage. European Journal of Pharmacology, 352(2–3), 165–169. https://doi.org/10.1016/S0014-2999(98)00353-7