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
- 来源:
- 关键词:4D MRIAcuteAddressAdultAgeAgingAgreementAlzheimer&aposs DiseaseAnimalsAnteriorAutomobile DrivingBlood VesselsBlood flowBrainBrain regionCerebral HypoxiaCerebrovascular CirculationCerebrovascular DisordersCerebrovascular PhysiologyCerebrovascular systemCerebrumClinicalDataDementiaDiabetes MellitusDiseaseDisease ProgressionEndotheliumEstradiolEstrogensEtiologyExhibitsFemaleFunctional disorderGoalsGonadal Steroid HormonesHealthHormonesHumanHypercapniaHypertensionHypoxiaKnowledgeLinkLong-Term CareMagnetic Resonance ImagingMediatingMethodsNitric OxideNitric Oxide SynthaseObesityOutcomePatientsPatternPerfusionPharmacologyPhysiologicalPopulationPremenopauseProstaglandin-Endoperoxide SynthaseProstaglandinsQuality of lifeRattusRegulationResearchResearch DesignResolutionRestRiskSex DifferencesSexual ReassignmentSignal TransductionStimulusStressSupplementationTechniquesTestingTestosteroneTherapeuticVasodilationVasodilator AgentsWomanactive controlanimal dataarterial spin labelingbasebrain circulationcerebral arterycerebrovascularclinically relevantcomorbiditydesigndisorder riskfemale sex hormonefunctional restorationgain of functionhigh riskhigh risk populationimproved functioningin vivoinsightjuvenile animalmalemenmultimodal datanovelphysiologic stressorpre-clinicalprogramsregional differenceresponsesexsexual dimorphismstroke risktechnological innovationvascular contributionsvasoconstrictionyoung adult
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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科研奖励数量(0)
会议论文数量(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:
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
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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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