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

Ying Han; Liping Ding; Xiang Cheng; Ming Zhao; Tong Zhao; Liang Guo; Xinyang Li; Yanan Geng; Ming Fan; Hong Liao; Lingling Zhu

doi:10.3389/fncel.2020.611764

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

Front Cell Neurosci. 2020 Dec 9:14:611764. doi: 10.3389/fncel.2020.611764. eCollection 2020.

Authors

Ying Han^{1

2}, Liping Ding³, Xiang Cheng¹, Ming Zhao¹, Tong Zhao¹, Liang Guo¹, Xinyang Li¹, Yanan Geng^{1

2}, Ming Fan^{1

2}, Hong Liao³, Lingling Zhu^{1

4}

Affiliations

¹ Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.
² Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
³ National Nanjing Center for Drug Screening, China Pharmaceutical University, Nanjing, China.
⁴ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

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.

Keywords: colitis; dextran sodium sulfate (DSS); hypoxia; microglia; neuroinflammation.