Estradiol exerts neuroprotective effects when administered after ischemic insult
Estradiol exerts neuroprotective effects when administered after ischemic insult
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DOI：
10.1161/01.str.31.3.745
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发表时间：
2000-03-01
期刊：
影响因子：
8.3
通讯作者：
Simpkins, JW
中科院分区：
文献类型：
--
作者：
Yang, SH;Shi, J;Simpkins, JW
背景和目的-17β-雌二醇(E_2)已有报道：TB发挥作用：在缺血损伤前给予的神经保护作用。本研究旨在确定雌激素在脑缺血后是否具有相同的作用，如果是，这个治疗窗保持多久，以及这种作用是否与脑血流的变化有关。方法-雌性SD大鼠造成永久性大脑中动脉阻塞(MCAO)。方案一：去卵巢后0.5(n=8)、1(n=6)、2(n=7)、3(n=6)、4(n=9)小时注射E_2(100µg/kg静脉注射后立即在硅胶橡胶管内皮下植入结晶E_2)：大脑中动脉结扎组(n=6)和去卵巢组(n=12)行大脑中动脉结扎术(MCAO)。MCAO后2d处死动物，2，3，5-三苯基四氮唑染色测定缺血灶体积。在方案2中，在缺血诱导0.5h后接受E2或赋形剂的动物组(INT组，n=6；OVX组，n=8，OVX+E2，n=6)在缺血前、1h、24h和48h监测脑血流量。结果：INT组和OVX组病变体积分别为20.9±-2.2%和21.8+/-1.2%。在大脑中动脉结扎后3小时内给药，可显著缩小病变体积。在MCAO后0.5、1、2、3、4小时注射E2，病变体积分别为6.3+/-0.5%、10.3+/-2.1%、11.8+/-1.8%、13.5+/-1.6%和17.9+/-2.8%。在MCAO后5分钟，INT和OVX动物的脑血流量分别下降到43.1+/-2.2%和25.4+/-1.0%。与OVX大鼠相比，给药后1h，OVX+E2组大鼠脑血流量无明显变化，但OVX+E2组给药后第1天和第2天脑血流量显著增加。结论给药时给予-E2具有神经保护作用；在永久性局灶性脑缺血模型中，给药后约3h为治疗窗；雌二醇的这种作用与脑血流量无即刻变化有关，但与脑血流量延迟增加有关。
Background and Purpose-17 beta-Estradiol (E2) has been reported:tb exert :neuroprotective effects when administered before an ischemic insult. This study was designed to determine whether E2 treatment after ischemia exerts the same effects and, if so, how long this therapeutic window remains open, and whether the effects are related to changes in cerebral blood flow (CBF).Methods-Female Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). In protocol 1, E2 was administered (100 mu g/kg IV followed immediately by subcutaneous implantation of crystalline E2 in a silicone elastomer tube) to ovariectomized females (OVX+E2) at 0.5 (n=8), 1 (n=6), 2 (n=7), 3 (n=6), or 4 (n=9) hours after: MCAO, Intact (INT; n=6) and ovariectomized females (OVX; n=12) were subjected to MCAO and received vehicle instead of E2. Two days after MCAO the animals were killed, and ischemic lesion volume was determined by 2,3,5-triphenyltetrazolium chloride staining. In protocol 2,CBF was monitored before and at 1, 24, and 48 hours in a group of animals receiving E2 or vehicle 0.5 hour after ischemia induction (INT, n=6; OVX, n=8 OVX+E2, n=6).Results-Lesion volume was 20.9+/-2.2% and 21.8+/-1.2% in the INT and OVX groups, respectively. E2 was found to decrease lesion volume significantly when administered within 3 hours after MCAO. The lesion volumes were 6.3+/-0.5%, 10.3+/-2.1%, 11.8+/-1.8%, 13.5+/-1.6%, and 17.9+/-2.8% when E2 was administered at 0.5, 1, 2, 3, or 4 hours after MCAO,: respectively. CBF decreased to 43.1+/-2.2% and 25.4+/-1.0% in the INT and OVX animals, respectively, at 5 minutes after MCAO. In comparison to OVX rats, CBF was not different at 1 hour after E2 administration but was increased significantly in the OVX+E2 group 1 and 2 days:after E2: administration.Conclusions-E2 exerts neuroprotective effects when administered;after ischemia, with a therapeutic window in a permanent focal cerebral ischemia model of approximately 3 hours; This effect of estradiol was associated with no immediate change in blood flow but with a delayed increase in CBF.