Effect of an antioxidant, Ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates
Effect of an antioxidant, Ebselen, on development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates
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DOI：
10.1016/s0090-3019(00)00168-3
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发表时间：
2000-04-01
影响因子：
--
通讯作者：
Kubota, T
中科院分区：
文献类型：
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作者：
Handa, Y;Kaneko, M;Kubota, T
蛛网膜下腔出血（SAH）后的氧化和/或自由基反应可能参与慢性脑血管痉挛的发展。抑制这些反应被认为是预防脑血管痉挛的治疗策略之一。我们研究了Ebselen，一种合成的硒有机化合物，表现出抗氧化谷胱甘肽过氧化物酶样活性，抑制自由基反应的脂质过氧化作用对慢性脑血管痉挛的发展在灵长类动物model.METHODS十七只猴子。通过在所有动物的右侧大脑中动脉和Willis环右侧周围引入血块来产生SAH。根据依布硒啉的剂量将猕猴随机分为3组：1）无剂量或未治疗组; 2）高剂量依布硒啉组; 3）低剂量依布硒啉组。SAH后高剂量组和低剂量组分别给予10 mg/Kg和5 mg/Kg，每日2次，共7 d。在诱导SAH前和SAH后第7天，在血管造影片上评估血管直径。血管造影显示与SAH前的基线值相比，右颈内动脉（伊卡）（减少38 ± 10%）和大脑中动脉（MCA）（减少56 ± 9.7%）的平均血管口径显著减少（p < 0.05）。在高剂量Ebselen治疗组中，右侧伊卡的平均血管口径减小百分比（16 +/- 11%）和MCA（28 +/- 9.5%）在第7天血管造影中，（p < 0.05）低于未治疗组，而低剂量依布硒啉组这些血管的平均减少百分比，结论：SAH后7天给予较大剂量依布硒啉可抑制慢性脑血管痉挛。结果提示，SAH后脂质过氧化引起的氧化或自由基反应可能参与了血管痉挛的发病机制，用药物如依布硒啉抑制这些反应可能对预防血管痉挛有良好的效果。(C)2000年，Elsevier Science Inc.
BACKGROUND Oxidation and/or free radical reactions after subarachnoid hemorrhage (SAH) may be involved in the development of chronic cerebral vasospasm. The inhibition of these reactions is thought to be one of the therapeutic strategies for prevention of cerebral vasospasm. We investigated the effect of Ebselen, a synthetic selenoorganic compound, which exhibits anti-oxidation by glutathione peroxidaselike activity to inhibit free radical reactions by lipid peroxidation on the development of chronic cerebral vasospasm in a primate model.METHODS Seventeen monkeys were used. SAH was produced by introduction of a blood clot around the right middle cerebral artery and the right side of the circle of Willis in all animals. The monkeys were randomly divided into three groups according to Ebselen dosage: 1) no dosage or non-treated group; 2) high-dose Ebselen group; and 3) low-dose Ebselen group. The drug was administered at 10 mg/Kg in the high-dose group and 5 mg/Kg in the low-dose group twice a day in each group for 7 days after SAH. The vessel diameter was evaluated on angiograms before the induction of SAH and at Day 7 following SAH.RESULTS In the untreated group, the angiograms showed significant (p < 0.05) reductions of the mean vessel caliber of the right internal carotid (ICA) (38 +/- 10% reduction) and the middle cerebral artery (MCA) (56 +/- 9.7%) compared with the baseline value before SAH. In the high-dose Ebselen-treated group, the mean percent reduction in vessel caliber of the right ICA (16 +/- 11%) and MCA (28 +/- 9.5%) on Day 7 angiograms were significantly (p < 0.05) lower than those in the nontreated group, whereas the mean percent reduction of these vessels in the low-dose Ebselen-treated group showed no significant difference compared with the untreated group.CONCLUSIONS Chronic cerebral vasospasm was inhibited in the animals in which a relatively large amount of Ebselen was administered for 7 days after SAH. The results suggest that the oxidation or free radical reaction by lipid peroxidation after SAH might be involved in the pathogenesis of vasospasm, and that inhibition of these reactions by drugs, such as Ebselen, may have a promising effect for prevention of vasospasm. (C) 2000 by Elsevier Science Inc.