1Department of Cognitive Science, Institute of Basic Medical Sciences, Beijing 100850, China
2Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China
3Beijing Institute for Brain Disorders, Beijing 100069, China
4Navy General Hospital of the PLA, Beijing 100048, China
5Air Force General Hospital of the PLA, Beijing 100142, China
Ming Fan (fanmingchina@126.com) & Lingling Zhu (linglingzhu@hotmail.com)

Abstract 

The hypobaric hypoxic environment in high-altitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear. Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury.

Keywords

Hypobaric hypoxia Inflammation, Brain injury, WIP1 phosphatase, Lipopolysaccharide

[SpringerLink]