The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic.
The neuroprotective effect of prostaglandin E2 EP1 receptor inhibition has a wide therapeutic window, is sustained in time and is not sexually dimorphic.
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DOI：
10.1038/jcbfm.2008.88
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发表时间：
2009-01
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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我们研究了前列腺素 E2 1 型受体 (EP1) 拮抗剂 SC51089 在小鼠大脑中动脉 (MCA) 闭塞产生的局灶性脑缺血模型中的神经保护作用的临床前特征。我们发现全身给予 SC51089（5 至 20 μg/kg；腹腔注射）可减少短暂（−50% ± 8%；n = 12；P < 0.05）或永久性（−39% ± 7%；n = 12；P < 0.05）MCA 闭塞产生的脑损伤。即使在缺血后 12 小时内给药，SC51089 仍然有效。在雄性和雌性小鼠中均观察到了保护作用，并且在诱导缺血后持续至少两周。损伤体积的减少与通过贝德森缺陷评分、吊线测试和角测试评估的神经功能的改善相关。这些数据提供了原理证明，证明 EP1 受体抑制是一种潜在有价值的神经保护策略，值得在人类中风的治疗应用中进行进一步的临床前研究。
We investigated the preclinical characteristics of the neuroprotective effect of the prostaglandin E2 type 1 receptor (EP1) antagonist SC51089 in models of focal cerebral ischemia produced by occlusion of the mouse middle cerebral artery (MCA). We found that systemic administration of SC51089 (5 to 20 μg/kg; i.p.) reduces the brain injury produced by transient (−50% ± 8%; n = 12; P < 0.05) or permanent (−39% ± 7%; n = 12; P < 0.05) MCA occlusion. SC51089 was effective even when administered up to 12 h after ischemia. The protective effect was observed both in male and female mice and was sustained for at least 2 weeks after induction of ischemia. The reduction in injury volume was associated with an improvement in neurological function assessed by the Bederson deficit score, the hanging wire test and the corner test. The data provide proof of principle that EP1 receptor inhibition is a potentially valuable strategy for neuroprotection that deserves further preclinical investigation for therapeutic application in human stroke.
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影响因子：
9.9
作者：
Barber, PA;Zhang, J;Buchan, AM
通讯作者：
Buchan, AM
影响因子：
8.3
作者：
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DOI：
10.1097/00004647-199809000-00012
发表时间：
1998-09-01
影响因子：
6.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.261323298
发表时间：
2001-12-18
影响因子：
11.1
作者：
Plesnila, N;Zinkel, S;Moskowitz, MA
通讯作者：
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影响因子：
11.2
作者：
O'Collins, VE;Macleod, MR;Howells, DW
通讯作者：
Howells, DW