BRAIN IMAGING IN ALTITUDE ILLNESS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项建议的目标是确定脑肿胀在急性高原反应(AMS)的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，运动过程中动脉血氧饱和度(SaO2)下降，以及轻微的液体滞留。我们最近还发现，与没有AMS的受试者相比，患有AMS的受试者血浆容量下降较小，细胞外水分增加较大。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，大多数大脑都会肿胀。我们的总体假设是，脑肿胀，包括脑含水量和血容量的增加，会导致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细胞、分子、遗传和生理反应在AMS病理生理学中的作用。这些新的和创新的方法包括：1)一氧化氮(NO)的产生；2)血管内皮生长因子(VEGF)；3)热休克因子/热休克蛋白72(HSF/HSP72)；以及4)血管紧张素转换酶(ACE)基因。我们还将首次对暴露于急性缺氧9小时的人类进行脑灌注压(ECPP)、颅内压(EICP)、脑血容量(CBV)、血脑屏障(BBB)通透性、脑含水量和颅髓体积的无创性测量。

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.