Neuroprotective efficacy of ebselen, an anti‐oxidant with anti‐inflammatory actions, in a rodent model of permanent middle cerebral artery occlusion
Neuroprotective efficacy of ebselen, an anti‐oxidant with anti‐inflammatory actions, in a rodent model of permanent middle cerebral artery occlusion
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依布硒啉（一种具有抗炎作用的抗氧化剂）在永久性大脑中动脉闭塞啮齿动物模型中的神经保护功效
DOI：
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发表时间：
1997
影响因子：
7.3
通讯作者：
I. Macrae
中科院分区：
文献类型：
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作者：
T. Takasago;E. E. Peters;D. Graham;H. Masayasu;I. Macrae
1本研究的目的是研究抗氧化剂和抗炎剂依布硒啉延迟治疗是否会减少永久性局灶性脑缺血啮齿动物模型的梗死体积。2在通过永久性闭塞左侧大脑中动脉（MCA）诱导脑缺血后30min和12 h，通过管饲法给予依布硒啉（10或30 mg kg-1）或溶剂。 MCA闭塞后24 h处死动物，通过定量组织病理学评价依布硒啉组和对照组的缺血性损伤体积。3依布硒啉在口服（灌胃）给药后迅速吸收，并在给药后1小时达到血浆峰值水平（10和30mg kg−1的血浆硒水平分别为0.68±0.04和0.84±0.1μg ml−1，而对照水平为0.51±0.02 μg kg−1）。 [4]低剂量依布硒啉（10 mg kg−1）治疗显著（P<0.01）减少了大脑半球和大脑皮层的梗死体积（与安慰剂组相比，分别减少了31.8%和36.7%）。 [5]高剂量依布硒啉（30 mg kg−1）的神经保护功效低于低剂量依布硒啉（10 mg kg−1）。 大脑半球缺血性损害体积减少23.7%（P<0.02），大脑皮质缺血性损害体积减少27.5%（P<0.01）。6在该模型中，两种剂量的依布硒啉（10、30 mg kg−1）对缺血最严重的尾状核没有治疗效果。 7自由基介导的损伤通常与缺血组织的再灌注有关。目前的结果表明，氧化损伤也是维持性（永久性）缺血模型中脑损伤的重要因素，并且依布硒啉可有效减轻这种自由基诱导的损伤。
1 The aim of this study was to investigate whether delayed treatment with the anti‐oxidant and anti‐inflammatory agent ebselen reduces the volume of infarction in a rodent model of permanent focal cerebral ischaemia. 2 Ebselen (10 or 30 mg kg−1) or vehicle was administered by gavage 30 min and 12 h after the induction of cerebral ischaemia by permanent occlusion of the left middle cerebral artery (MCA). Animals were killed 24 h following MCA occlusion, and the volumes of ischaemic damage in the ebselen and control groups were evaluated by quantitative histopathology. 3 Ebselen was quickly absorbed following oral (gavage) administration and reached peak levels in the plasma by 1 h post‐administration (plasma selenium level of 0.68±0.04 and 0.84±0.1 μg ml−1 for 10 and 30 mg kg−1, respectively, compared to control level of 0.51±0.02 μg kg−1). 4 Treatment with the lower dose of ebselen (10 mg kg−1) significantly (P<0.01) reduced the volume of infarction in the cerebral hemisphere and cerebral cortex (by 31.8% and 36.7%, respectively compared with the placebo group). 5 The neuroprotective efficacy of the higher dose ebselen (30 mg kg−1) was less than that of the lower dose ebselen (10 mg kg−1). The volume of ischaemic damage in the cerebral hemisphere was reduced by 23.7% (P<0.02), and cerebral cortex by 27.5% (P<0.01). 6 Both doses of ebselen (10, 30 mg kg−1) had no therapeutic efficacy on the caudate nucleus, where ischaemia was most severe, in this model. 7 Free radical‐mediated injury is normally associated with reperfusion of ischaemic tissue. The present results suggest that oxidative injury is also a significant contributor to brain damage in models of maintained (permanent) ischaemia and that ebselen is effective in attenuating this free radical‐induced damage.
DOI：
10.1111/j.1748-1716.1994.tb09816.x
发表时间：
1994-11
期刊：
Acta physiologica Scandinavica
影响因子：
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作者：
Qi Zhao;Kerstin Pahlmark;Maj-lis Smith;B. Siesjö
通讯作者：
Qi Zhao;Kerstin Pahlmark;Maj-lis Smith;B. Siesjö
影响因子：
8.3
作者：
Naoki Matsumiya;R. Koehler;J. Kirsch;R. Traystman
通讯作者：
Naoki Matsumiya;R. Koehler;J. Kirsch;R. Traystman