Zhou, Y, Huang, X, Zhao, T, Qiao, M, Zhao, X, Zhao, M, Xu, L, Zhao, Y, Wu, L, Wu, K, Chen, R, Fan, M and Zhu, L (2017) Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice. Brain, Behavior, and Immunity, 64. pp. 226-275. ISSN 0889-1591

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Abstract High altitude cerebral edema (HACE) is a life-threatening illness that develops during the rapid ascent to high altitudes, but its underlying mechanisms remain unclear. Growing evidence has implicated inflammation in the susceptibility to and development of brain edema. In the present study, we investigated the inflammatory response and its roles in HACE in mice following high altitude hypoxic injury. We report that acute hypobaric hypoxia induced a slight inflammatory response or brain edema within 24 h in mice. However, the lipopolysaccharide (LPS)-induced systemic inflammatory response rapidly aggravated brain edema upon acute hypobaric hypoxia exposure by disrupting blood-brain barrier integrity and activating microglia, increasing water permeability via the accumulation of aquaporin-4 (AQP4), and eventually leading to impaired cognitive and motor function. These findings demonstrate that hypoxia augments LPS-induced inflammation and induces the occurrence and development of cerebral edema in mice at high altitude. Here, we provide new information on the impact of systemic inflammation on the susceptibility to and outcomes of HACE.

Item Type: Article
Additional Information: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://doi.org/10.1016/j.bbi.2017.04.013 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Lipopolysaccharide (LPS),Blood-brain barrier (BBB), High altitude cerebral edema (HACE),Inflammation
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 20 Apr 2017 15:38
Last Modified: 07 Apr 2021 09:16
URI: https://eprints.keele.ac.uk/id/eprint/3291

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