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。稳定的脑血流对调节呼吸至关重要，尤其是在给人体带来最大压力的运动期间。尽管这种关系涉及的生理机制在很大程度上尚不清楚，但呼吸引起的二氧化碳变化和大脑血液流动密切相关。然而，最近，我们已经证明，在运动过程中，大脑血流量会增加，更重要的是，它在调节呼吸方面起着关键作用。这些发现，以及在研究人脑血液动力学方面的技术进步，激发了人们对研究休息和运动期间脑血流调节机制的兴趣。有趣的是，当健康的人上升到高海拔时，通常会出现显著的通气量增加和异常周期性呼吸的发展。虽然机制在很大程度上还不清楚，但我们的初步数据表明，脑血流的变化可能是这种情况的基础。通过结合静息和运动时复杂的黄金标准脑成像技术，在有和没有药物干预的情况下，该研究计划旨在检查：1)大脑血液流动影响休息和运动期间呼吸的机制；2)这些控制机制在高海拔暴露期间发生变化的程度；3)长期暴露在高海拔地区可能导致对调节血液流动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身上进行探索，这是一个在高海拔地区出生和长大的群体，世代如此。解决这项提案中概述的新目标将提供关于应激(例如，锻炼)期间的脑血流和适应这种应激(例如，在高海拔地区)的新信息。重要的是，这些研究将扩大对控制脑血流和呼吸控制的基本机制的理解。

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.