Brain Microcirculation, Platelets, and Sex Hormones

Rosenblum, William

Abstract

The arterioles and venules on the cerebral surface will be injured, the carotid artery will be injured, and arachidonate will be infused into the carotid artery. These 3 techniques will result in platelet aggregates appearing in cerebral vessels, and this will be monitored in living animals (mice) by direct observation of cerebral surface vessels via the microscope, and by histologic study of the brain (rats, mice). This investigation focusses on the influence of gender and sex hormones on aggregation in the directly injured cerebral vessels and on aggregates produced by injected arachidonate, or arising as emboli from an injured carotid. The latency of aggregation, the numbers of aggregates or vessels involved by aggregates, will be monitored. The effect of gender or hormones in vivo will be compared with and/or related to the influence of these variables on platelet aggregability in vitro and on the production of antiaggregant materials by vessel wall. The effect of gender and sex on the response to antiaggregatory drugs will also be determined. The responses of cerebral vessels will be compared with that of the mesentery or the renal vascular bed. The studies will provide data relevant to the presently contradictory literature concerning the detrimental effect of either male or female hormones in diseases dependent in whole or part, upon platelet aggregation. Among these diseases are transient ischemic attacks. The data will also be relevant to the question of preferential benefit in males, of antiplatelet therapies such as aspirin.