Estrogen reduces leukocyte adhesion in the cerebral circulation of female rats

In this study the authors addressed the hypothesis that estrogen (i.e., 17beta-estradiol) acts to repress leukocyte adhesion. The experiments involved comparing leukocyte adhesion in cerebral venules in vivo, in intact ovariectomized and 17beta-estradiol-treated (100 microg/kg/day for 1 week) ovariectomized female rats using topical applications of the adhesion-promoting drug, phorbol 12-myristate 13-acetate (PMA). Adherent Rhodamine-6G-labeled leukocytes were viewed through a closed cranial window using intravital microscopy/videometry. Leukocyte dynamics were recorded at baseline and after each dose of PMA. The PMA was suffused (1.0 mL/min) at increasing concentrations (0.01, 0.1, and 1.0 micromol/L, 15 minutes at each level). A videotape record of each experiment was made for subsequent analysis of leukocyte adhesion. The data showed that the percentage venular area occupied by adherent leukocytes at baseline was significantly greater in the ovariectomized compared to the intact and 17beta-estradiol-treated groups (12.2%, 3.4%, and 4.2% respectively). That relationship was maintained during PMA treatments to the extent that the percentage venular area occupied by adherent leukocytes increased to 26.4% in the untreated ovariectomized group compared to 14.4% and 11.3% in the intact and 17beta-estradiol-treated groups, respectively. In conclusion, the authors found chronic estrogen depletion enhances leukocyte adhesion in the rat cerebral circulation. Estrogen repletion in such animals is accompanied by a significant reduction in leukocyte adhesion. These findings could, at least in part, account for the ischemic brain damage seen in ovariectomized versus intact females, and the restored neuroprotection observed upon 17beta-estradiol treatment reported in earlier studies.