Window of opportunity: estrogen as a treatment for ischemic stroke.
Window of opportunity: estrogen as a treatment for ischemic stroke.
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DOI：
10.1016/j.brainres.2013.01.023
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发表时间：
2013-06-13
期刊：
影响因子：
2.9
通讯作者：
Yang SH
中科院分区：
文献类型：
--
作者：
Liu R;Yang SH
近20年来，雌激素作为神经保护剂对包括脑卒中在内的神经退行性疾病的作用越来越受到人们的关注。雌激素的神经保护作用已在缺血性中风的体外和体内模型中得到充分证实。然而，迄今为止进行的主要临床试验已经引起了人们对雌激素替代疗法在绝经后妇女中的保护作用的关注。这种差异可能部分是由于实验性中风研究和临床试验之间的误译。虽然主要的实验研究使用急性治疗范式测试雌激素对缺血性卒中的保护作用，但临床试验主要集中在雌激素替代疗法对一级和二级卒中预防的作用，这在实验性卒中研究中尚未得到充分解决。虽然主要的临床试验表明，雌激素替代疗法有不良反应，并提出了长期雌激素替代疗法预防中风的关注，这些都不适合评估急性雌激素治疗对中风保护的潜在影响。雌激素在神经血管单位中的良好作用及其与重组组织纤溶酶原激活剂（rtPA）的潜在相互作用使其成为与rtPA联合治疗缺血性卒中急性期的候选药物。另一方面，“关键期”假说和新出现的“生物标志物窗口”假说表明，在缺血性脑卒中的实验研究中，许多临床相关因素被低估了。复制临床症状的缺血性脑卒中模型的建立和应用对于进一步评价雌激素治疗缺血性脑卒中的疗效至关重要，这可能为未来的临床试验提供关键信息。
The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue plasminogen activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the “critical period” and newly emerged “biomarkers window” hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials.
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