BRAIN IMAGING IN ALTITUDE ILLNESS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 “这项提案的目标是确定脑肿胀在急性高原病（AMS）病理生理学中的作用。我们最近发现，运动导致AMS症状严重程度增加>3倍，运动期间动脉血氧饱和度（SaO 2）下降，以及轻微的液体潴留。我们最近还发现，与没有AMS的受试者相比，患有AMS的受试者血浆体积略有下降，细胞外水大幅上升。在进一步的研究中，磁共振成像显示，当人类上升到高海拔时，大多数大脑都会膨胀。我们的总体假设是，脑肿胀，包括脑水和血容量升高，导致AMS的症状。我们的方法是使用一些新的和创新的技术来剖析AMS的病理生理学中的细胞，分子，遗传和生理反应的作用。新的和创新的方法包括测量人类急性缺氧1）一氧化氮（NO）的生产; 2）血管内皮生长因子（VEGF）; 3）热休克因子/热休克蛋白72（HSF/HSP 72）;和4）血管紧张素转换酶（ACE）基因型。我们还将首次对暴露人群的脑灌注压（eCPP）、颅内压（eICP）、脑血容量（CBV）、血脑屏障（BBB）通透性、脑水和颅脊髓体积进行无创测量 急性缺氧9小时。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 'The goal of this proposal is to determine the role of brain swelling in the pathophysiology of acute mountain sickness (AMS). We recently showed that exercise caused a >3 fold rise in AMS symptom severity, a drop in arterial oxygen saturation (SaO2) during exercise, and slight fluid retention. We also recently showed that subjects ill with AMS had a small drop in plasma volume and a large rise in extracellular water compared to those that remained free of AMS. In further studies, magnetic resonance imaging revealed that most brains swell when humans ascend to high altitude. Our overall hypothesis is that brain swelling, which can include elevated brain water and blood volume, causes the symptoms of AMS. Our approach is to use several new and innovative technologies to dissect the role of cellular, molecular, genetic and physiological responses in the pathophysiology of AMS. The new and innovative approaches include measurement in humans acutely deprived of oxygen of 1) nitric oxide (NO) production; 2) vascular endothelial growth factor (VEGF); 3) heat shock factor/heat shock protein72 (HSF/HSP72); and 4) angiotensin converting enzyme (ACE) genotype. We will also make the first noninvasive measurements of cerebral perfusion pressure (eCPP), intracranial pressure (eICP), cerebral blood volume (CBV), blood-brain barrier (BBB) permeability, brain water and craniospinal volumes in humans exposed to acute hypoxia for 9 hrs.