Frontiers of hypoxia research: acute mountain sickness

Traditionally, scientists and clinicians have explored peripheral physiolog ical responses to acute hypoxia to explain the pathophysiological processes that lead to acute mountain sickness (AMS) and high-altitude cerebral edem a (HACE). After more than 100 years of investigation, little is yet known a bout the fundamental causes of the headache and nausea that are the main sy mptoms of AMS. Thus, we review the evidence supporting a change in focus to the role of the central nervous system in AMS. Our justification is (i) th at the symptoms of AMS and HACE are largely neurological, (ii) that HACE is considered to be the end-stage of severe AMS and was recently identified a s a vasogenic edema, opening the door for a role for blood-brain barrier pe rmeability in AMS, (iii) that new, non-invasive techniques make measurement of brain water levels and cerebral blood volume possible and (iv) that the available experimental evidence and theoretical arguments support a signif icant role for brain swelling in the pathophysiology of AMS. We believe tha t an examination of the responses of the central nervous system to acute hy poxia will reveal important new pathophysiological processes that may help explain AMS and HACE.