Neuroprotective effects of female gonadal steroids in reproductively senescent female rats
Neuroprotective effects of female gonadal steroids in reproductively senescent female rats
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DOI：
10.1161/01.str.31.1.161
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发表时间：
2000-01-01
期刊：
影响因子：
8.3
通讯作者：
Hurn, PD
中科院分区：
文献类型：
--
作者：
Alkayed, NJ;Murphy, SJ;Hurn, PD
背景和目的——年轻的成年雌性大鼠在实验性脑卒中后的梗死比同龄的雄性大鼠要小。幼龄动物缺血性脑损伤的这种性别差异在卵巢切除术后消失，可通过雌激素替代恢复。我们试图确定与年龄匹配的雄性大鼠相比，中年、生殖衰老的雌性大鼠的缺血性脑损伤是否仍然较小，并测试卵巢类固醇对实验性脑卒中后雌性大鼠脑损伤的影响。方法：选取4组16月龄Wistar大鼠（雄性[n=9]，雌性[n=9]，未经处理的雌性[n=9]，以及经17 -雌二醇[25 μ g微丸，皮下给药7天；n=9]或孕酮[10 mg微丸，皮下给药7天；n=9]预处理的雌性），采用腔内细丝技术阻断大脑中动脉2小时，再灌注22小时。在缺血和早期再灌注过程中监测生理指标和激光多普勒脑皮质灌注。在一个单独的队列中，男性（n=3），未经治疗的女性（n=3），接受17 -雌二醇预处理的女性（n=3），以及接受孕酮预处理的女性（n=3），通过[C-14]碘安替比林放射自显像测量缺血末期区域脑血流。结果：正如预测的那样，中年雄性和雌性大鼠的梗死面积没有差异。男性和女性同侧大脑皮层皮层梗死分别为21+/-5%和31+/-6%，纹状体梗死分别为44+/-7%和43+/-5%。雌激素和黄体酮均可减少生殖衰老女性的皮质梗死（雌激素和黄体酮治疗组分别为5+/-2%和16+/-4%）。雌激素组纹状体梗死发生率为31%（±6%），黄体酮组纹状体梗死发生率低于对照组（±6%）。与缺血前基线相比，激光多普勒脑皮质灌注的相对变化和缺血末期区域脑血流的绝对变化不受激素治疗的影响。结论：年轻成年雌性大鼠对缺血性脑损伤的保护作用在中年雌性生殖衰老后消失，卵巢激素减轻生殖衰老雌性大鼠脑卒中损伤的机制与血流无关。这些发现支持激素替代疗法在绝经后妇女中风损伤预防中的作用。
Background and Purpose-Young adult female rats sustain smaller infarcts after experimental stroke than age-matched males. This sex difference in ischemic brain injury in young animals disappears after surgical ovariectomy and can be restored by estrogen replacement. We sought to determine whether ischemic brain injury continues to be smaller in middle-aged, reproductively senescent female rats compared with age-matched males and to test the effect of ovarian steroids on brain injury after experimental stroke in females.Methods-Four groups of 16-month old Wistar rats (males [n=9], untreated females [n=9], and females pretreated with 17 beta-estradiol [25-mu g pellets administered subcutaneously for 7 days; n=9] or progesterone [10-mg pellets administered subcutaneously for 7 days; n=9] were subjected to 2 hours of middle cerebral artery occlusion with the intraluminal filament technique, followed by 22 hours of reperfusion. Physiological variables and laser-Doppler cerebral cortical perfusion were monitored throughout ischemia and early reperfusion. In a separate cohort of males (n=3), untreated females (n=3), females pretreated with 17 beta-estradiol (n=3), and females pretreated with progesterone (n=3), end-ischemic regional cerebral blood flow was measured by [C-14]iodoantipyrine autoradiography.Results-As predicted, infarct size was not different between middle-aged male and female rats. Cortical infarcts were 21+/-5% and 31+/-6% of ipsilateral cerebral cortex, and striatal infarcts were 44+/-7% and 43+/-5% of ipsilateral striatum in males and females, respectively. Both estrogen and progesterone reduced cortical infarct in reproductively senescent females (5+/-2% and 16+/-4% in estrogen- and progesterone-treated groups. respectively, compared with 31+/-6% in untreated group), Striatal infarct was smaller in the estrogen- but not in the progesterone-treated group. Relative change in laser-Doppler cerebral cortical perfusion from preischemic baseline and absolute end-ischemic regional cerebral blood flow were not affected by hormonal treatments.Conclusions-We conclude that the protection against ischemic brain injury found in young adult female rats disappears after reproductive senescence in middle-aged females and that ovarian hormones alleviate stroke injury in reproductively senescent female rats by a blood flow-independent mechanism. These findings support a role for hormone replacement therapy in stroke injury prevention in postmenopausal women.