Transcriptomic profiling and targeted validation reveal molecular mechanisms of oxygen therapy in high-altitude cerebral injury

作者：Xiaojie Hu, Xuedong Bai, Shuyi Pan, Hongxia Li · 发表于：Frontiers in Neuroscience · 年份：2026 · DOI：10.3389/fnins.2026.1738756 · 研究领域：High Altitude and Hypoxia、Heme Oxygenase-1 and Carbon Monoxide、Cancer, Hypoxia, and Metabolism

Background: Exposure to high-altitude hypoxia is associated with an increased risk of impaired brain structure and function, with oxidative stress and neuroinflammation widely recognized as key mechanisms involved. In this context, hyperbaric oxygen therapy is considered a potential intervention; however, the mechanism by which it affects cerebral function changes caused by high-altitude exposure remains to be further elucidated. Objective: This study aims to explore and compare the therapeutic effects of normobaric oxygen (NBO) and hyperbaric oxygen (HBO) on high-altitude cerebral injury (HACI), and to elucidate the molecular mechanisms underlying their neuroprotective effects using transcriptomic profiling and targeted validation. Methods: A mouse model of high-altitude cerebral injury was established using a hypobaric hypoxia chamber. Mice were exposed to a simulated altitude of 7,000 m (approximately 9.8% O₂ at 0.47 ATA) for 3 consecutive days to induce severe hypoxia. Animals were divided into four groups: Control (Con), High-Altitude exposure (HH), post-HH treated with normobaric oxygen (NBO; 100% O₂ at 1.0 ATA for 1 h daily for 3 days), and post-HH treated with hyperbaric oxygen (HBO; 100% O₂ at 2.0 ATA for 1 h daily for 3 days). Brain tissues were analyzed using H&E staining, RNA sequencing (RNA-seq), Western blotting for key pathway proteins, immunofluorescence for glial cell activation, and ELISA for inflammatory cytokines. Oxidative stress markers (SOD, MDA, GSH, N...