Human cerebral blood flow regulation: sex, mechanism, and stress differences

人类脑血流调节:性别、机制和应激差异

基本信息

  • 批准号:
    10407466
  • 负责人:
  • 金额:
    $ 60.71万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-06-01 至 2025-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Cerebrovascular disease is the third leading killer in the U.S., and contributes to decreased quality of life and increased long-term care spending. The risk of cerebrovascular disease is inversely associated with resting cerebral blood flow (CBF). Men exhibit a lower resting CBF and have twice the risk of cerebrovascular disease when compared to premenopausal women. The ability of cerebral vessels to respond to challenges is also inversely related to disease risk, and may be useful in identifying at-risk patients pre-clinically. However, these studies are often confounded by aging and/or comorbidities, and the associations provide little insight into physiologic mechanisms responsible for sexually dimorphic cerebrovascular disease risk. Conversely, animal studies use supraphysiologic levels of hormone treatment in primarily young animals, which limits the translational relevance of animal CBF mechanisms. While there is general agreement that estrogen is protective in healthy adults, the basic impact of sex, and physiologic fluctuations in sex hormones, on mechanisms of CBF control remains unclear. The overall goal of this research program is to investigate the mechanisms which actively control cerebral blood flow (CBF) in humans, particularly how men and women differ in control mechanisms on a regional basis throughout the brain circulation. We propose to study CBF control mechanisms in healthy younger (18-40 yrs) adult men and women. The overall hypothesis is that female sex and sex hormones contribute to larger stress-induced increases in CBF, due to greater prostanoid (COX) and nitric oxide (NOS) dilation. A key technological innovation of this proposal derives from multi-mode, high-resolution, flow sensitive MRI to quantify CBF at macro- and microvascular levels, at rest, and in response to environmental challenges. Additionally, the research design allows us to quantify sex differences in two vascular control mechanisms across all brain regions. Our preliminary data demonstrate: hypoxic cerebral vasodilation is 60-100% higher in women compared to men, COX inhibition reduces dilation in women but not men, NOS inhibition reduces vasodilation more in women, and hypoxic vasodilation is increased in women during early luteal cycle, in part to greater COX-mediated vasodilation. We also will use sex hormone suppression, followed by single hormone addition, to systematically study the impacts on CBF control in both sexes. We have substantial preliminary findings that support our hypotheses, and have integrated physiologic, pharmacologic, and MRI approaches to test our hypotheses. This state-of-the- art approach will yield previously unattainable insight into not only maintaining CBF, but actively controlling it during physiologic demands for increased flow. These novel, high resolution, regionally- specific, sex-specific, and mechanism-specific findings will serve as a knowledge platform, for designing sex-specific CBF studies in high risk disease populations (e.g. diabetes, hypertension, Alzheimer’s) which exhibit strong sex-specific etiology and important vascular contributions.
项目总结/文摘

项目成果

期刊论文数量(0)
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WILLIAM G SCHRAGE其他文献

WILLIAM G SCHRAGE的其他文献

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{{ truncateString('WILLIAM G SCHRAGE', 18)}}的其他基金

Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
  • 批准号:
    10650368
  • 财政年份:
    2020
  • 资助金额:
    $ 60.71万
  • 项目类别:
Insulin resistance, cognitive health, and perfusion of the adolescent brain
胰岛素抵抗、认知健康和青少年大脑灌注
  • 批准号:
    9980475
  • 财政年份:
    2019
  • 资助金额:
    $ 60.71万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8185406
  • 财政年份:
    2011
  • 资助金额:
    $ 60.71万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8515512
  • 财政年份:
    2011
  • 资助金额:
    $ 60.71万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8688332
  • 财政年份:
    2011
  • 资助金额:
    $ 60.71万
  • 项目类别:
Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
  • 批准号:
    8323220
  • 财政年份:
    2011
  • 资助金额:
    $ 60.71万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7587863
  • 财政年份:
    2009
  • 资助金额:
    $ 60.71万
  • 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
  • 批准号:
    7770776
  • 财政年份:
    2009
  • 资助金额:
    $ 60.71万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6710162
  • 财政年份:
    2002
  • 资助金额:
    $ 60.71万
  • 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
  • 批准号:
    6447034
  • 财政年份:
    2002
  • 资助金额:
    $ 60.71万
  • 项目类别:

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