Prolonged opportunity for neuroprotection in experimental stroke with selective blockade of cyclooxygenase-2 activity.

Prolonged opportunity for neuroprotection in experimental stroke with selective blockade of cyclooxygenase-2 activity.
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DOI:
10.1016/j.brainres.2009.05.020
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发表时间:
2009-07-07
期刊:
影响因子:
2.9
通讯作者:
Graham SH
Graham SH
中科院分区:
医学3区
文献类型:
--
作者:
Ahmad M;Zhang Y;Liu H;Rose ME;Graham SH

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选择性环氧合酶(考克斯)-2抑制剂伐地昔布的治疗后效应,在大鼠模型的暂时局灶性缺血进行了研究。伐地昔布在不影响血清血栓素B2的剂量下降低基底脑前列腺素E2浓度,与选择性考克斯-2效应一致。大脑中动脉阻断90 min造成大鼠局灶性脑缺血,Western blot和免疫细胞化学检测缺血后4 h和24 h皮质神经元内考克斯-2蛋白表达增加。大鼠在脑缺血前15 min或缺血后1.5、3和6 h分别给予溶剂或伐地昔布。缺血后24 h处死大鼠,测定脑梗死体积。戊地昔布治疗与脑缺血前15分钟、脑缺血后1.5或3小时(而非6小时)的梗死体积减少相关。手术期间生理参数无差异。缺血后1.5小时给予伐地昔布,与溶剂处理组和对侧非缺血皮质相比,缺血半暗带皮质中前列腺素E2的浓度显著降低。这些结果表明,考克斯-2抑制与伐地昔布是有效的,当启动之前和之后大脑中动脉闭塞。
The post-treatment effects of the selective cyclooxygenase (COX)-2 inhibitor, valdecoxib, were investigated in a rat model of temporary focal ischemia. Valdecoxib reduced basal brain prostaglandin E2 concentrations at dosages that did not affect serum thromboxane B2, consistent with a selective COX-2 effect. Temporary focal cerebral ischemia was produced in rats by middle cerebral artery occlusion for 90 min. There was increased expression of COX-2 protein detected by Western blot and immunocytochemistry within neurons in the ischemic cortex at 4 and 24 h after ischemia. Rats were treated with vehicle or valdecoxib 15 min before or 1.5, 3 and 6 h after cerebral ischemia. Rats were sacrificed and brain infarction volume determined 24 h after ischemia. Valdecoxib treatment was associated with a decrease in infarction volume when administered 15 min before, and 1.5 or 3 h but not 6h after cerebral ischemia. There were no differences in physiological parameters during the procedure. Valdecoxib administered at 1.5 h after ischemia significantly reduced the concentrations of prostaglandin E2 in ischemic penumbral cortex as compared to the vehicle-treated group and contralateral non-ischemic cortex. These results suggest that COX-2 inhibition with valdecoxib is effective when initiated both before and after middle cerebral artery occlusion.
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