Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Abstract

The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.

• Authors: Ying Han, Liping Ding, Xiang Cheng, Ming Zhao, Tong Zhao, Liang Guo, Xinyang Li, Yanan Geng, Ming Fan, Hong Liao, Lingling Zhu
• Journal: Frontiers in cellular neuroscience (Front Cell Neurosci) Vol. 14 Pg. 611764 ( 2020) ISSN: 1662-5102 [Print] Switzerland
• PMID: 33362475 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Han, Ding, Cheng, Zhao, Zhao, Guo, Li, Geng, Fan, Liao and Zhu.