Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats
Coumestrol has neuroprotective effects before and after global cerebral ischemia in female rats
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DOI：
10.1016/j.brainres.2012.07.025
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发表时间：
2012-09-20
期刊：
影响因子：
2.9
通讯作者：
Netto, Carlos Alexandre
中科院分区：
文献类型：
--
作者：
Castro, Cibele Canal;Pagnussat, Aline S.;Netto, Carlos Alexandre
在心脏骤停或心脏手术过程中出现的全脑缺血导致海马CA 1区神经元高度选择性的延迟性死亡。植物雌激素是存在于人类饮食中的天然存在的植物衍生化合物，被认为是选择性雌激素受体（ER）调节剂。植物雌激素香豆雌酚是一种强效异黄酮，对ER-α和ER-β的结合亲和力与17 b-雌二醇相当。本研究探讨了香豆雌酚保护去卵巢大鼠全脑缺血模型海马神经元的假设。卵巢切除大鼠进行全脑缺血（10分钟）或假手术，并接受了一个单一的脑室内或外周输液的20微克香豆雌酚，20微克雌二醇或车辆缺血前1小时或Oh，3小时，6小时或24小时后再灌注。雌二醇和香豆雌酚在所有给药时间均提供了显著的神经保护作用，但在缺血损伤后24小时给予雌二醇除外。在E2或香豆雌酚给药之前，动物接受广谱ER拮抗剂ICI 182，780（50 μ g）或溶媒冰冷输注到侧脑室。雌激素受体拮抗剂废除雌二醇保护，与经典的ER的作用一致。相比之下，ICI 182，780仅部分逆转香豆雌酚的神经保护作用，表明除了经典ER外，其他细胞介质可能也很重要。需要进一步的研究来确定介导香豆雌酚神经保护作用的分子靶点和这种植物雌激素在成熟神经系统中的治疗潜力。(C)2012爱思唯尔有限公司版权所有。
Global ischemia arising during cardiac arrest or cardiac surgery causes highly selective, delayed death of hippocampal CA1 neurons. Phytoestrogens are naturally occurring plant-derived compounds that are present in the human diet and are considered selective estrogen receptor (ER) modulators. The phytoestrogen coumestrol is a potent isoflavonoid, with binding affinities for both ER-alpha and ER-beta that are comparable to those of 17b-estradiol. The present study examined the hypothesis that coumestrol protects hippocampal neurons in ovariectomized rats in a model of cerebral global ischemia. Ovariectomized rats were subjected to global ischemia (10 min) or sham surgery and received a single intracerebroventricular or peripheral infusion of 20 mu g of coumestrol, 20 mu g of estradiol or vehicle 1 h before ischemia or Oh, 3 h, 6 h or 24 h after reperfusion. Estradiol and coumestrol afforded significant neuroprotection in all times of administration, with the exception of estradiol given 24 h after the ischemic insult. Animals received icy infusion of the broad-spectrum ER antagonist ICI 182,780 (50 mu g) or vehicle into the lateral ventricle just before the E2 or coumestrol administration. The ER antagonist abolished estradiol protection, consistent with a role of classical ERs. In contrast, ICI 182,780 effected only partial reversal of the neuroprotective actions of coumestrol, suggesting that other cellular mediators in addition to classical ERs may be important. Additional research is needed to determine the molecular targets mediating the neuroprotective action of coumestrol and the therapeutic potential of this phytoestrogen in the mature nervous system. (C) 2012 Elsevier B.V. All rights reserved.