Citation

Lafuente JV, Bermudez G, Camargo-Arce L, Bulnes S. CNS Neurol. Disord. Drug Targets 2016; 15(9): 1188-1197.

Affiliation

University of the Basque Country (UPV/EHU) - LaNCE, Department of Neuroscience, Leioa, Spain.

Copyright

(Copyright © 2016, Bentham Science Publishers)

DOI

unavailable

PMID

27667557

Abstract

Cerebral syndromes related to high altitude exposure are becoming more frequent as the number of trips to high altitudes has increased in the last decade. The commonest symptom is headache, followed by acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), which can be fatal. The pathophysiology of these syndromes is not fully comprehended. The classical "tight-fit hypothesis" defends the fact that there are some anatomical variations that would obstruct the sinovenous outflow and worsen the vasogenic edema and intracranial hypertension reactive to hypoxia. This could explain microhemorrhages seen in autopsies. However, recent MR studies have demonstrated some components of cytotoxic edema in HACE absent in AMS, suggesting a dysfunction in the water balance at the cellular level. Currently, the "red-ox theory" stands up for trigemino-vascular system (TVS) activation by free radicals formed after hypoxia and the consecutive oxidative stress cascades. Apart from the TVS activation, free radicals can also provoke membrane destabilisation mediated by lipid peroxidation, inflammation, and local HIF-1a and VEGF activation, resulting in gross blood-brain barrier (BBB) dysfunction. Besides, alterations in endothelial cells, such as increased pinocytotic vesicles and disassemble of the interendothelial tight junctions proteins may also increase capillar permeability with subsequent swelling of the astrocyte end-feet. In conclusion, although the pathophysiology of AMS and HACE is not completely understood, recent evidences propose a multifactorial entity, with brain swelling and a deep compromise at BBB considered to play an important role. A better understanding is crucial to reduce and prevent BBB alterations during high altitude exposure.

Language: en