A method for establishing the high-altitude cerebral edema (HACE) model by acute hypobaric hypoxia in adult mice.

Abstract Background Exposure to acute hypobaric hypoxia (AHH) during ascent to high altitudes (>3500 m) is one of the main causes of acute mountain sickness (AMS) and high-altitude cerebral edema (HACE). Therefore, the aim of this study was to develop a model of HACE. New methods We developed a model of HACE in mice using a decompression chamber with rapid ascent speed. Results Healthy male C57BL/6 mice were randomly divided into the control group and the AHH group. The AHH group was housed in a decompression chamber (at a velocity of 50 m/s within 5 min to 6000 m). Compared with the controls, brain water content was increased in the early stage (within 24 h) in the AHH group. After 72 h of exposure to AHH, there was a higher BBB permeability observed. In addition, the brain structure showed significant widening of the pericellular spaces and a dilatation of the cortical blood vessels after exposure to AHH, and some of the neurons appeared shrunken with darkly stained pyknotic nuclei, resulting in neuronal structural damage. Further, exposure to AHH also decreased cognitive function in the mice. Comparison with existing methods At present, there are no simple and rapid mouse models to study this syndrome in terms of its genetic basis, gene polymorphisms and susceptibility. Conclusion Our findings show that AHH can increase BBB permeability and lead to cerebral edema in mice; thus, we provide an effective and stable model of HACE in mice.