Hydroxyl radical generation after the third hour following ischemia contributes to brain damage

Hiroyuki Takamatsu, Kazunao Kondo, Yasuhiko Ikeda, Kazuo Umemura

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27 Citations (Scopus)


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-K1 in the brain tissue and plasma following 10 mg/kg intravenous bolus treatment of conscious rats, we investigated the neuroprotective effect of EPC-K1 in the middle cerebral artery occlusion model. A single intravenous bolus of EPC-K1 was given immediately, 3 or 6 h after ischemia, and cerebral brain damage was measured 24 h after ischemia. When EPC-K1 was injected 3 h after ischemia, a significant (P<0.01) reduction of cerebral brain damage was observed. EPC-K1 delivered 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.

Original languageEnglish
Pages (from-to)165-169
Number of pages5
JournalEuropean Journal of Pharmacology
Issue number2-3
Publication statusPublished - 10-07-1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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