Huang Xin, Zhou Yanzhao, Zhao Tong, Han Xue, Qiao Meng, Ding Xuefeng, Li Dahu, Wu Liying, Wu Kuiwu, Zhu Ling-ling, Fan Ming
Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China.
Department of Brain Protection and Plasticity, Institute of Basic Medical Sciences, Beijing 100850, China; Co-innovation Center of Neuro-regeneration, Nantong University, Nantong, JS 226001, China.
J Neurosci Methods. 2015 Apr 30;245:178-81. doi: 10.1016/j.jneumeth.2015.02.004. Epub 2015 Feb 19.
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.
We developed a model of HACE in mice using a decompression chamber with rapid ascent speed.
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.
At present, there are no simple and rapid mouse models to study this syndrome in terms of its genetic basis, gene polymorphisms and susceptibility.
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.
在攀登至高海拔地区（>3500米）时暴露于急性低压缺氧（AHH）是急性高原病（AMS）和高原脑水肿（HACE）的主要原因之一。因此，本研究的目的是建立一种HACE模型。
我们使用具有快速上升速度的减压舱在小鼠中建立了HACE模型。
健康雄性C57BL/6小鼠被随机分为对照组和AHH组。AHH组置于减压舱中（在5分钟内以50米/秒的速度升至6000米）。与对照组相比，AHH组在早期（24小时内）脑含水量增加。暴露于AHH 72小时后，观察到血脑屏障（BBB）通透性更高。此外，暴露于AHH后，脑结构显示细胞周隙明显增宽，皮质血管扩张，一些神经元出现皱缩，核固缩且染色深，导致神经元结构损伤。此外，暴露于AHH还降低了小鼠的认知功能。
目前，尚无简单快速的小鼠模型来从遗传基础、基因多态性和易感性方面研究该综合征。
我们的研究结果表明，AHH可增加小鼠血脑屏障通透性并导致脑水肿；因此，我们提供了一种有效且稳定的小鼠HACE模型。
