Integration between breathing and brain blood flow

循环系统最重要的任务是维持血液流向大脑。稳定的脑血流量对于帮助调节呼吸至关重要，特别是在对人体产生最大单一压力的运动期间。虽然这种关系所涉及的生理机制在很大程度上是未知的，呼吸引起的二氧化碳和脑血流量的变化是密切相关的。然而，最近，我们已经证明，大脑血流量增加运动过程中，重要的是，在调节呼吸中起着关键作用。这些发现，以及研究人脑血流动力学的技术进展，激发了人们对研究休息和运动时脑血流调节机制的兴趣。有趣的是，当健康人上升到高海拔时，通气量显著增加以及异常周期性呼吸的发展通常会发生。虽然其机制在很大程度上是未知的，但我们的初步数据表明，脑血流的改变可能是这种情况的基础。通过结合先进的金标准脑成像技术在休息和运动期间，有和没有药物干预，这项研究计划的目的是检查：1）脑血流影响的机制，在休息和运动期间的呼吸; 2）在何种程度上这些控制机制被改变，在暴露于高海拔地区;以及3）长时间暴露于高海拔可能导致对调节血流和呼吸的机制的生物适应。后一个目标将在尼泊尔夏尔巴人中进行探索，夏尔巴人是一个在高海拔地区出生和长大的多代人。 解决该提案中概述的新目标将提供有关压力期间脑血流的新信息（例如，锻炼）和对这种压力的适应（例如，在高海拔）。重要的是，这些研究将拓宽对脑血流和呼吸控制基本机制的理解。

The most important task for the circulatory system is to maintain blood flow to the brain. Stable brain blood flow is crucial to help regulate breathing, especially during exercise which provides the greatest single stress on the human body. Although the physiological mechanisms involved in this relationship are largely unknown, breathing-induced changes in carbon dioxide and brain blood flow are tightly linked. Recently, however, we have demonstrated that brain blood flow increases during exercise and, importantly, plays a critical role in regulating breathing. These findings, as well as the technological evolutions in studying human brain hemodynamics, has ignited interest in studying regulatory mechanisms of brain blood flow at rest and during exercise. Interestingly, marked increases in ventilation as well as the development of abnormal periodic breathing commonly occur when healthy humans ascend to high altitude. Although the mechanisms are largely unknown, our preliminary data indicate that alterations in brain blood flow may underpin the condition. By combining sophisticated gold-standard brain imaging techniques at rest and during exercise, with and without pharmacological intervention, this program of research aims to examine: 1) the mechanisms by which brain blood flow influences the breathing at rest and during exercise; 2) the extent to which these control mechanisms are altered during exposure to high altitude; and 3) how long term exposure to high altitude may lead to biological adaptations to the mechanisms that regulate blood flow and breathing. The latter aim will be explored in the Nepalese Sherpa, a population born and bred at high altitude over many generations. Addressing the novel aims outlined in this proposal will provide new information about brain blood flow during stress (e.g., exercise) and adaptation to such stress (e.g., at high altitude). Importantly, these studies will broaden understanding of the fundamental mechanisms governing both brain blood flow and breathing control.