Santizo R A, Anderson S, Ye S, Koenig H M, Pelligrino D A
Neuroanesthesia Research Laboratory, Department of Anesthesiology, University of Illinois at Chicago, Chicago, IL 60607, USA.
Stroke. 2000 Sep;31(9):2231-5. doi: 10.1161/01.str.31.9.2231.
Recent findings indicate that estrogen (ie, 17beta-estradiol [E(2)]) provides neuroprotection in models of transient global and focal ischemia. Enhanced postischemic leukocyte adhesion and infiltration have been linked to neuropathology in the brain as well as other tissues. We recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions.
We compared leukocyte adhesion in pial venules in vivo in intact, ovariectomized (OVX), and E(2)-treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and hemorrhagic hypotension) and reperfusion. Adherent rhodamine-6G-labeled leukocytes were viewed through a closed cranial window with the use of intravital microscopy. Leukocyte adhesion was measured before ischemia and at different times after reperfusion.
Before ischemia, leukocyte adhesion (measured as a percentage of venular area occupied by adherent leukocytes) was 2 to 3 times greater in OVX versus intact or E(2)-treated OVX rats (7.0%, 3.4%, and 2.2%, respectively). This difference disappeared at 120 minutes of reperfusion, when comparable levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfusion (11.6% and 12.9%, respectively), while the other 2 groups showed significantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E(2)-treated OVX rats).
Present results demonstrate that estrogen modulates leukocyte adhesion in the cerebral circulation after transient forebrain ischemia. This effect suggests that decreased leukocyte adhesion may be an important mechanism in estrogen-mediated neuroprotection.
最近的研究结果表明，雌激素（即17β-雌二醇[E₂]）在短暂性全脑缺血和局灶性缺血模型中具有神经保护作用。缺血后白细胞黏附和浸润增强与脑及其他组织的神经病理学有关。我们最近发现，在静息状态下，雌激素可减少雌性大鼠脑循环中的白细胞黏附。
我们比较了完整、去卵巢（OVX）和接受E₂治疗的OVX雌性大鼠在短暂性前脑缺血（右侧颈总动脉闭塞30分钟并伴有出血性低血压）及再灌注后，软脑膜微静脉中白细胞的黏附情况。通过封闭的颅骨视窗利用活体显微镜观察罗丹明-6G标记的黏附白细胞。在缺血前及再灌注后的不同时间测量白细胞黏附情况。
缺血前，OVX大鼠的白细胞黏附（以黏附白细胞所占微静脉面积的百分比衡量）比完整或接受E₂治疗的OVX大鼠高2至3倍（分别为7.0%、3.4%和2.2%）。在再灌注120分钟时，这种差异消失，此时所有组中白细胞黏附增强的水平相当。在OVX大鼠中，再灌注4小时和6小时后白细胞黏附仍保持升高（分别为11.6%和12.9%），而其他两组水平显著较低（完整大鼠为5.0%和5.8%，接受E₂治疗的OVX大鼠为7.0%和7.2%）。
目前的结果表明，雌激素可调节短暂性前脑缺血后脑循环中的白细胞黏附。这种作用提示白细胞黏附减少可能是雌激素介导的神经保护作用的重要机制。
