Department of Basic Science, Educational and Research Center for Pharmacy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan.
Int J Mol Sci. 2022 Feb 11;23(4):2010. doi: 10.3390/ijms23042010.
Hepatic encephalopathy is a major cause of liver failure. However, the pathophysiological role of ventricle enlargement in brain edema remains unclear. Here, we used an acute hepatic encephalopathy mouse model to examine the sequential pathological changes in the brain associated with this condition. We collected tissue samples from experimental animals treated with ammonium acetate at 3 and 24 h post-injection. Despite the normalization of the animal's ammonia levels, samples taken at 24 h after injection exhibited distinct enlargement of lateral ventricles. The choroid plexus samples obtained at 3 h post-ammonium acetate treatment indicated enlargement; however, this swelling was reduced at the later timepoint. The aquaporin-1 proteins that regulate the choroid plexus were localized both in the apical membrane and the cytoplasm of the epithelia in the control; however, they translocated to the apical membranes of the epithelia in response to ammonia treatment. Therefore, severe acute hepatic encephalopathy induced by ammonium acetate administration caused enlargement of the ventricles, through swelling of the choroid plexus and aquaporin-1 transport and aggregation within the apical membranes.
肝性脑病是肝衰竭的主要原因。然而，脑室扩大在脑水肿中的病理生理作用尚不清楚。在这里，我们使用急性肝性脑病小鼠模型来研究与这种情况相关的脑内连续病理变化。我们从用醋酸铵处理的实验动物中采集组织样本，分别在注射后 3 小时和 24 小时进行采集。尽管动物的氨水平恢复正常，但在注射后 24 小时采集的样本显示出明显的侧脑室扩大。在醋酸铵处理后 3 小时采集的脉络丛样本显示出扩张；然而，在稍后的时间点，这种肿胀减少了。调节脉络丛的水通道蛋白-1 蛋白在对照组中定位于上皮的顶膜和细胞质中；然而，它们在受到氨处理时会向上皮的顶膜转移。因此，醋酸铵给药引起的严重急性肝性脑病导致脑室扩大，通过脉络丛肿胀以及水通道蛋白-1 在顶膜中的转运和聚集。
