Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice

- Inflammation may play vital roles in high altitude cerebral edema is proposed.
- Hypoxia augments LPS-induced systemic inflammation and neuroinflammation.
- Combination of hypoxia exposure and LPS injection rapidly induces cerebral edema.
- Combination of hypoxia exposure and LPS injection induces blood-brain barrier leakage by disrupting tight junctions.
- Combination of hypoxia exposure and LPS injection induces cognitive and motor dysfunction.

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.