Effects of estrogen on leukocyte adhesion after transient forebrain ischemia

Background and Purpose-Recent findings indicate that estrogen (ie, 17 beta- 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. W e recently showed that estrogen reduces leukocyte adhesion in the cerebral circulation of female rats during resting conditions. Methods-We compared leukocyte adhesion in pial venules in vivo in intact, o variectomized (OVX), and E-2-treated OVX female rats subjected to transient forebrain ischemia (30-minute right common carotid artery occlusion and he morrhagic hypotension) and reperfusion. Adherent rhodamine-6G-labeled leuko cytes were viewed through a closed cranial window with the use of intravita l microscopy. Leukocyte adhesion was measured before ischemia and at differ ent times after reperfusion. Results-Before ischemia, leukocyte adhesion (measured as a percentage of ve nular 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 comparabl e levels of enhanced leukocyte adhesion were observed in all groups. In OVX rats, leukocyte adhesion remained elevated after 4 and 6 hours of reperfus ion (11.6% and 12.9%, respectively), while the other 2 groups showed signif icantly lower levels (5.0% and 5.8% for intact rats and 7.0% and 7.2% for E -2-treated OVX rats). Conclusions-Present results demonstrate that estrogen modulates leukocyte a dhesion in the cerebral circulation after transient forebrain ischemia. Thi s effect suggests that decreased leukocyte adhesion may be an important mec hanism in estrogen-mediated neuroprotection.