Stimulation of prostaglandin E2-EP3 receptors exacerbates stroke and excitotoxic injury
Stimulation of prostaglandin E2-EP3 receptors exacerbates stroke and excitotoxic injury
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DOI：
10.1016/j.jneuroim.2006.12.012
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发表时间：
2007-03-01
影响因子：
3.3
通讯作者：
Dore, Sylvain
中科院分区：
文献类型：
--
作者：
Ahmad, Muzamil;Ahmad, Abdullah Shafique;Dore, Sylvain
在小鼠脑缺血和兴奋性损伤模型上，研究了PGE（2）EP 3受体对脑损伤大小的影响。用选择性EP 3激动剂ONO-AE-248治疗显著且剂量依赖性地增加了大脑中动脉闭塞模型中的梗死面积。在单独的实验中，用ONO-AE-248预处理加重了由N-甲基-D-天冬氨酸诱导的急性兴奋性毒性引起的损伤。相反，EP 3的基因缺失提供了对N-甲基-D-天冬氨酸诱导的毒性的保护。结果表明，PGE（2）通过刺激EP 3受体，可以促进与环氧合酶相关的毒性，拮抗这种受体可以用于治疗，以防止中风和兴奋性毒性诱导的脑损伤。(c)2007 Elsevier B. V.保留所有权利。
The effect of PGE(2) EP3 receptors on injury size was investigated following cerebral ischemia and induced excitotoxicity in mice. Treatment with the selective EP3 agonist ONO-AE-248 significantly and dose-dependently increased infarct size in the middle cerebral artery occlusion model. In a separate experiment, pretreatment with ONO-AE-248 exacerbated the lesion caused by N-methyl-D-aspartic acid-induced acute excitotoxicity. Conversely, genetic deletion of EP3 provided protection against N-methyl-D-aspartic acid-induced toxicity. The results suggest that PGE(2), by stimulating EP3 receptors, can contribute to the toxicity associated with cyclooxygenase and that antagonizing this receptor could be used therapeutically to protect against stroke- and excitotoxicity-induced brain damage. (c) 2007 Elsevier B.V. All rights reserved.