Wang Q, Santizo R, Baughman V L, Pelligrino D A, Iadecola C
Department of Anesthesiology, Neuroanesthesia Research Laboratory, University of Illinois at Chicago, USA.
Stroke. 1999 Mar;30(3):630-7. doi: 10.1161/01.str.30.3.630.
Estrogen-related neuroprotection in association with animal models of transient forebrain and focal ischemia has been documented in several recent reports. Some of those studies indicated that part of that benefit was a function of improved intraischemic vasodilating capacity. In the present study we examined whether chronic estrogen depletion and repletion affected ischemic neuropathology through perfusion-independent mechanisms.
Normal, ovariectomized (OVX), and OVX female rats treated with 17beta-estradiol (E2) were subjected to 30 minutes of transient forebrain ischemia (right common carotid occlusion plus hemorrhagic hypotension) and reperfusion. Neurological function and brain histopathology were assessed over the 72-hour recovery period. In all rats, preischemic and intraischemic cortical cerebral blood flow (CBF) levels were monitored with laser-Doppler flowmetry. In additional rats, CBF changes in the striatum and hippocampus were also monitored with laser-Doppler flowmetry probes and radiolabeled microspheres. In each experiment, the level of ischemia was targeted to a 75% to 80% reduction in cortical CBF.
The similarity in ischemic severity among groups was supported by measurements of comparable patterns of electroencephalographic power changes during the ischemic period. Compared with normal females, OVX rats showed diminished neurological outcomes and more severe histopathology in the hippocampus and striatum. Two-week treatment of OVX rats with E2 was accompanied by postischemic neuropathological changes similar to those seen in normal females. Intraischemic CBF reductions in the hippocampus and striatum were similar in all groups (to 35% to 50% of the preischemic value) but significantly less than the cortical CBF reductions.
These findings indicate that estrogen provides ischemic neuroprotection through mechanisms unrelated to improvement of intraischemic cerebral perfusion.
最近有几份报告记录了雌激素相关的神经保护作用与短暂性前脑和局灶性缺血动物模型的关联。其中一些研究表明，这种益处部分是缺血期血管舒张能力改善的作用。在本研究中，我们研究了慢性雌激素缺乏和补充是否通过与灌注无关的机制影响缺血性神经病理学。
对正常、去卵巢（OVX）以及用17β-雌二醇（E2）治疗的OVX雌性大鼠进行30分钟的短暂性前脑缺血（右颈总动脉闭塞加出血性低血压）和再灌注。在72小时的恢复期内评估神经功能和脑组织病理学。在所有大鼠中，用激光多普勒血流仪监测缺血前和缺血期皮质脑血流量（CBF）水平。在另外的大鼠中，还用激光多普勒血流仪探头和放射性标记微球监测纹状体和海马体中的CBF变化。在每个实验中，缺血程度的目标是使皮质CBF降低75%至80%。
缺血期脑电图功率变化模式的测量结果支持了各组缺血严重程度的相似性。与正常雌性大鼠相比，OVX大鼠的神经功能结果较差，海马体和纹状体的组织病理学更严重。用E2对OVX大鼠进行两周治疗后，缺血后神经病理学变化与正常雌性大鼠相似。所有组中海马体和纹状体的缺血期CBF降低情况相似（降至缺血前值的35%至50%），但明显低于皮质CBF的降低。
这些发现表明，雌激素通过与改善缺血期脑灌注无关的机制提供缺血性神经保护。
