17Χ-Estradiol extends ischemic thresholds and exerts neuroprotective effects in cerebral subcortex against transient focal cerebral ischemia in rats
17Χ-Estradiol extends ischemic thresholds and exerts neuroprotective effects in cerebral subcortex against transient focal cerebral ischemia in rats
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DOI：
10.1016/j.brainres.2003.07.006
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发表时间：
2003-12-12
期刊：
影响因子：
2.9
通讯作者：
Simpkins, JW
中科院分区：
文献类型：
--
作者：
Fan, T;Yang, SH;Simpkins, JW
雌激素的神经保护作用在大脑皮层中得到了一致的证实，但在皮层下区域却没有。在本研究中，短暂的大脑中动脉闭塞（MCAO）诱导不同的持续时间，雌激素治疗对大脑皮层和皮层下的保护作用进行了评估。在去卵巢大鼠中诱导MCAO 30、40或60 min。在MCAO前2 h用17 β-雌二醇（E2）或溶剂（OVX）处理动物，并在指定的MCAO持续时间后24 h处死动物。采用氯化三苯基四氮唑（2，3，5-triphenyltetrazolium chloride）染色、苏木素伊红染色、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）染色评价缺血性损伤。E2治疗降低了总缺血性病变面积的大小并延迟了其出现，并在很大程度上阻止了皮质中的TUNEL染色。在皮层下，E2治疗预防了30分钟组的缺血性病变，减少了40分钟组的病变面积，但对60分钟组的缺血性病变面积没有影响。E2处理显著减少皮质下区的凋亡细胞数在30和40分钟，但在60分钟的MCAO。这项研究表明，雌激素治疗可以保护大脑皮层下的严重程度依赖性的方式，这表明，缺乏保护作用的雌激素治疗在皮层下不是由于缺乏雌激素受体。此外，本研究表明，雌激素可作为一种神经保护剂，以延长溶栓治疗窗和延长脑循环干预的时间，神经外科手术。(C)2003 Elsevier B. V.保留所有权利。
Neuroprotective effects of estrogens are demonstrated consistently in the cerebral cortex, but not in subcortical areas. In the present study, transient middle cerebral artery occlusions (MCAO) were induced for various duration, and protective effects of estrogen treatment on the cerebral cortex and subcortex were evaluated. MCAO was induced for 30, 40 or 60 min in ovariectomized rats. Animals were treated with 17beta-estradiol (E2) or vehicle (OVX) 2 h before MCAO and sacrificed 24 h after the indicated duration of MCAO. Ischemic lesion was evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. E2 treatment reduced the magnitude and delayed the appearance of the total ischemic lesion area and largely prevented TUNEL staining in the cortex. In the subcortex, E2 treatment prevented the ischemic lesion in the 30-min group, reduced lesion area in the 40-min group, but had no effect on ischemic lesion area in the 60-min group. E2 treatment significantly decreased apoptotic cell number in the subcortical area at 30 and 40 min, but not at 60 min of MCAO. This study demonstrated that estrogen treatment can protect the cerebral subcortex in a severity-dependent manner, suggesting that the lack of protective effects of estrogen treatment in the subcortex is not due to the lack of estrogen receptors. Further, this study indicates that estrogens could be used as a neuroprotectant to prolong the therapeutic window of thrombolysis and prolong the time of cerebral circulation intervention for neurosurgical procedure. (C) 2003 Elsevier B.V. All rights reserved.