Markers of Cerebrovascular Dysfunction in Women at Risk

项目III的长期目标是识别早期的非侵入性成像和血液生物标志物 脑血管功能障碍与认知健康。具体地说，该项目的目标是定义和 项目I和项目II的参与者的特点：1)经颅脑微血管扩张能力 多普勒超声；2)血载微泡的细胞来源、含量和血栓形成潜能 使用流式细胞术和使用血小板分泌和激活分析的血小板功能；以及 3)血源性微泡特性与血小板功能、脑功能的关系 微血管扩张能力与脑组织结构和认知的变化，如项目I和II所定义。 我们小组的三个独立观察结果为该项目提供了基础，并可能与 荷尔蒙状态、血液传播元素、血管功能和认知。第一，通过血液传播的数量 血栓前微囊随着绝经后雌激素水平的降低而增加；第二，血管的舒张量 更年期妇女脑微血管的数量减少；第三，血小板数量 微团聚体与脑白质高信号呈正相关，与认知呈负相关 绝经后36个月内的表现。这一提议的实验将定义来源和 血液成分和微泡的同时特征，以及脑微血管的特征 心血管疾病和认知功能减退高危女性的舒张性能力 子痫前期或绝经期雌激素缺乏。这项研究的结果是独立的，但与 项目一和项目二是关于一个历史上女性具体性别状况的SCOR的总体主题 子痫前期或更年期激素状态通过改变脑血管功能来影响认知。 此外，对血小板和微泡特征的评估提供了潜在的机制 脑微血管扩张能力可以被调节，并且更普遍地与脑血管疾病的发生有关 女性的心血管疾病。

The long-term goal of Project III is to identify non-invasive imaging and blood biomarkers of eariy cerebrovascular dysfunction and cognitive health. Specifically, aims of this project are to define and characterize in participants of Projects I and II: 1) cerebral microvascular dilatory capacity using transcranial Doppler ultrasonography; 2) the cellular origin, content, and thrombotic potential of blood-borne microvesicles using flow cytometry and platelet functions using assays for platelet secretion and activation; and 3) relationships among characteristics of blood-borne microvesicles, platelet functions, and cerebral microvascular dilatory capacity with changes in brain stmeture and cognition, as defined in Projects I and II. Three independent observations from our group provide the basis for this project and potential links among hormonal status, blood-borne elements, vascular function, and cognition. First, numbers of blood-borne prothrombotic microvesicles increase with decreases in estrogen at menopause; second, the dilatory capacity of the cerebral microvasculature decreases in women at menopause; and third, numbers of platelet microaggregates correlate positively with brain white matter hyperintensities and negatively with cognitive performance within 36 months of menopause. Experiments of this proposal will define sources and characteristics of blood elements and microvesicles simultaneously, together with cerebral microvascular dilatory capacity in women at risk for cardiovascular disease and cognitive decline based on either a history of preeclampsia or estrogen deficiency at menopause. Results of this study stand on their own but link results of Projects I and II to the overarching theme oif the SCOR of how female sex-specific conditions of a history preeclampsia or menopausal hormonal status affect cognition through changes in cerebrovascular function. Furthermore, assessment of platelet and microvesicle characteristics provides potential mechanisms by which cerebral microvascular dilatory capacity could be modulated and associate more generally with development of cardiovascular disease in women.