Blood-Brain Barrier Changes in High Altitude

作者：José Vicente Lafuente, Garazi Bermudez, Lorena Camargo-Arce, Susana Bulnes · 发表于：CNS & Neurological Disorders - Drug Targets · 年份：2016 · DOI：10.2174/1871527315666160920123911 · 被引用次数：73 · 研究领域：High Altitude and Hypoxia、Heme Oxygenase-1 and Carbon Monoxide、Neuroscience of respiration and sleep

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 understood. The classical "tight-fit hypothesis" posits that there are some anatomical variations that would obstruct the sinovenous outflow and worsen vasogenic edema and intracranial hypertension reactive to hypoxia. This could explain microhemorrhages seen in autopsies. However, recent magnetic resonance imaging studies have demonstrated some components of cytotoxic edema in HACE absent in AMS, suggesting a dysfunction in water balance at the cellular level. Currently, the "red-ox theory" supports trigemino-vascular system activation by free radicals formed after hypoxia and the consequent oxidative stress cascades. Apart from trigemino-vascular system activation, free radicals can also provoke membrane destabilisation mediated by lipid peroxidation, inflammation, and local hypoxia inducible factor-1α and vascular endothelial growth factor activation, resulting in gross blood-brain barrier (BBB) dysfunction. Besides alterations in endothelial cells such as increased pinocytotic vesicles and disassembly of interendothelial tight junction proteins, capillary permeability may also increase with subsequent swelling of astrocyte end-feet. ...