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.
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