Regulatory mechanisms of cerebral blood flow in humans

人体脑血流的调节机制

• 批准号: RGPIN-2020-04057
• 负责人: Smirl, Jonathan
• 金额: $ 1.75万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757906
• 关键词: Regulatory; mechanisms; cerebral; blood; flow

Maintaining cerebral blood flow (CBF) regulation is of critical importance for humans, both to preserve consciousness and enable healthy neural development. CBF control occurs via a series of regulatory processes broadly sorted into three facets: cerebral autoregulation (CA); neurovascular coupling (NVC); cerebrovascular reactivity (CVR). In contrast to the wealth of knowledge on adult males in these areas, there is very limited literature with respect to adolescent populations, biological sex and cardiorespiratory fitness level comparisons across all ages. It is also relatively unknown how a bout of exercise actively influences CA, NVC and CVR regulatory mechanisms. The LONG-TERM VISION of my research program is to better understand these fundamental CBF regulatory processes throughout the pediatric-to-adult aging process in males and females. In addition, my research program will examine the influence exercise has upon this measures both in terms of acute bouts as well as the chronic impact related to cardiorespiratory fitness levels. Over the next five-years, my lab will address three short-term research objectives: The first SHORT-TERM OBJECTIVE will be to quantify the CA, NVC and CVR mechanisms across the adolescence developmental period in both males and females. Overall CBF decreases from ~10 years to adulthood, however the specific mechanisms underlying this reduction remain unclear. Results from my research group will provide insight into the underlying factors affecting CBF regulation throughout adolescence. The second SHORT-TERM OBJECTIVE will identify the extent various forms and intensities of acute exercise bouts has upon the CA, NVC and CVR responses across the healthy aging spectrum. Virtually all CBF based studies include a statement for subjects to abstain from exercise for a period of 12-24 hours prior to participating, yet there is no empirical evidence in the literature demonstrating exercise alters CA, NVC and CVR mechanisms to validate this common assumption. My research group will identify the duration a bout of exercise affects CBF regulatory mechanisms. The final SHORT-TERM OBJECTIVE will be to identify the influence various cardiovascular fitness levels affect the CA, NVC and CVR responses across the healthy aging spectrum within both male and female biological sexes. Historically, this research field has overlooked these even though both biological sex and cardiovascular fitness levels have profound impacts on cardiovascular physiology (e.g. glucose tolerance, blood pressure control, neurofeedback control). This objective will identify the contributing roles sex and cardiovascular fitness have on CBF regulatory mechanisms. Overall the vision for my research group is to aid in furthering our comprehension of healthy human brain development and the broader implications of acute and chronic exercise training on this fundamental process.

维持脑血流量（CBF）调节对人类至关重要，既可以保持意识，也可以促进健康的神经发育。CBF控制通过一系列调节过程发生，大致分为三个方面：脑自动调节（CA）;神经血管耦合（NVC）;脑血管反应性（CVR）。与这些领域中关于成年男性的丰富知识相反，关于青少年人口、生物性别和所有年龄段心肺健康水平比较的文献非常有限。运动如何积极影响CA，NVC和CVR调节机制也相对未知。 我的研究计划的长期愿景是更好地了解这些基本的CBF调节过程，在男性和女性的儿科到成人的衰老过程。此外，我的研究计划将研究运动对这一措施的影响，包括急性发作以及与心肺健康水平相关的慢性影响。在接下来的五年里，我的实验室将致力于三个短期研究目标：第一个短期目标将是量化男性和女性青少年发育期的CA，NVC和CVR机制。总体CBF从~10岁到成年期减少，然而这种减少的具体机制仍不清楚。从我的研究小组的结果将提供深入了解整个青春期影响CBF调节的潜在因素。 第二个短期目标将确定各种形式和强度的急性运动对整个健康老龄化谱的CA，NVC和CVR反应的影响程度。几乎所有基于CBF的研究都包括受试者在参与前12-24小时内放弃运动的声明，但文献中没有实证证据表明运动改变CA，NVC和CVR机制来验证这一常见假设。我的研究小组将确定一轮运动的持续时间影响CBF调节机制。 最终短期目标是确定各种心血管健康水平对男性和女性生物性别健康老龄化范围内CA、NVC和CVR反应的影响。从历史上看，这个研究领域忽视了这些，即使生物性别和心血管健康水平对心血管生理学（例如葡萄糖耐量，血压控制，神经反馈控制）有深远的影响。这一目标将确定性别和心血管健康对CBF调节机制的贡献作用。 总的来说，我的研究小组的愿景是帮助我们进一步理解健康的人类大脑发育以及急性和慢性运动训练对这一基本过程的更广泛影响。