Neuroprotective effects of estradiol in newborn female rat hippocampus
Neuroprotective effects of estradiol in newborn female rat hippocampus
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DOI：
10.1016/j.devbrainres.2004.03.006
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
McCarthy, MM
中科院分区：
文献类型：
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作者：
Hilton, GD;Ndubuizu, AN;McCarthy, MM
由于缺氧/缺血事件导致的围产期脑损伤与包括谷氨酸在内的过量兴奋性神经递质的释放有关。我们以前已经证明，给予谷氨酸受体激动剂海人酸(KA)到出生后第0天(PN0)和PN1大鼠会导致选择性地损害雌性大鼠的齿状回。用性腺类固醇雌二醇预处理可防止KA对雌性齿状回的损伤。目的：阐明雌二醇对新生女性的神经保护作用的细胞机制。我们分别在体内和体外使用了雌激素受体拮抗剂他莫昔芬和ICI182,780。外周给予跨越血脑屏障的三苯氧胺，可阻止雌二醇介导的神经保护作用，以对抗KA诱导的齿状回损伤。高选择性雌激素受体拮抗剂ICI182,780不会从外周渗透到脑内，也可以阻止雌二醇对KA诱导的海马神经元死亡的保护作用，但只是在损伤的时间过程的后期。这些数据表明，雌二醇对KA诱导的损伤的神经保护作用是由雌激素受体介导的，但可能包括一种不在受体上拮抗的额外机制。(C)2004爱思唯尔B.V.保留所有权利。
Perinatal brain injury, consequent to hypoxic/ischemic events, is associated with the release of excess excitatory neurotransmitters, including glutamate. We have previously shown that administration of a glutamate receptor agonist, kainic acid (KA), to postnatal day 0 (PN0) and PN1 rats results in damage selective to the dentate gyrus of females. Pretreatment with the gonadal steroid estradiol prevents KA-induced damage to the female dentate gyrus. To begin to elucidate the cellular mechanism of the neuroprotective effects of estradiol in neonatal females. we have employed the estrogen receptor antagonists Tamoxifen and ICI 182,780 in vivo and in vitro, respectively. Peripheral administration of Tamoxifen, which crosses the blood-brain barrier, prevented estradiol-mediated neuroprotection against KA-induced damage in the dentate gyrus. The highly selective estrogen receptor antagonist ICI 182,780, which does not penetrate into the brain from the periphery, also prevented estradiol's protective effects on KA-induced cell death in cultured hippocampal neurons but only late in the time course of injury. The data suggest that the neuroprotection afforded by estradiol against KA-induced injury in the female is estrogen receptor mediated but may include an additional mechanism that is not antagonized at the receptor. (C) 2004 Elsevier B.V. All rights reserved.