Estrogen reduces leukocyte adhesion in the cerebral circulation of female rats

In this study the: authors addressed the hypothesis that estrogen (i.e., 17 beta-estradiol) acts to repress leukocyte adhesion. The experiments involv ed comparing leukocyte adhesion in cerebral venules in vivo, in intact ovar iectomized and 17 beta-estradiol-treated (100 mu g/kg/day for 1 week) ovari ectomized 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 mic roscopy/videometry. Leukocyte dynamics were recorded at baseline and after each dose of PMA. The PMA was suffused (1.0 mL/min) at increasing concentra tions (0.01, 0.1, and 1.0 mu mol/L, 15 minutes at each level). A videotape record of each experiment was made for subsequent analysis of leukocyte adh esion. The data showed that the percentage venular area occupied by adheren t leukocytes at baseline was significantly greater in the ovariectomized co mpared to the intact and 17 beta-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 leukoc ytes increased to 26.4% in the untreated ovariectomized group compared to 1 4.4% and 11.3% in the intact and 17 beta-estradiol-treated groups, respecti vely. In conclusion, the authors found chronic estrogen depletion enhances leukocyte adhesion in the rat cerebral circulation, Estrogen repletion in s uch animals is accompanied by a significant reduction in leukocyte adhesion . These findings could, at least in part, account for the ischemic brain da mage seen in ovariectomized versus intact females, and the restored neuropr otection observed upon 17 beta-estradiol treatment reported in earlier stud ies.