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(Landmark Ed)"],"abstract":"<jats:p>Background: High-altitude hypobaric hypoxia is known to impair cognitive function, but the underlying mechanistic role of impaired redox homeostasis in this context remains incompletely understood. This study investigated whether acute hypobaric hypoxia induces oxidative stress and redox dysregulation in the hippocampus, and whether oxygen enrichment can mitigate these impairments by restoring redox homeostasis. Methods: Spatial memory was assessed using the Morris water maze. Additionally, hippocampal morphology, redox status (including glutathione\/oxidized glutathione [GSH\/GSSG], the reduced nicotinamide adenine dinucleotide\/oxidized nicotinamide adenine dinucleotide [NADH\/NAD+], and the reduced nicotinamide adenine dinucleotide phosphate\/oxidized nicotinamide adenine dinucleotide phosphate [NADPH\/NADP+] ratios, as well as antioxidant enzyme activity levels), and associated molecular pathways were analyzed. Results: Following 3 days of hypoxia exposure, rats exhibited impaired spatial memory retention, increased neuronal apoptosis, and reduced neuronal viability in the hippocampal cornu ammonis 1 [CA1] region. The hippocampus displayed significantly altered redox status, characterized by elevated GSH\/GSSG, NADH\/NAD+, and NADPH\/NADP+ ratios, upregulated antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPX]), and decreased superoxide levels. These changes are consistent with an adaptive nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response and a shift toward a reductive state. Notably, oxygen enrichment rescued cognitive deficits, attenuated neuronal apoptosis, and normalized redox ratios and the microtubule-associated protein 1A\/1B-light chain 3-II\/microtubule-associated protein 1A\/1B-light chain 3-I (LC3B-II\/ LC3B-I) ratio. Conclusions: Hypoxia-induced redox dysregulation is closely associated with cognitive impairment. Oxygen enrichment alleviates these deficits by modulating the Nrf2-mediated adaptive response and restoring redox homeostasis, thereby supporting further investigation of oxygen enrichment as a potential neuroprotective strategy.<\/jats:p>","DOI":"10.31083\/fbl54346","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:21:51Z","timestamp":1790698911000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting Reductive Stress With Oxygen Enrichment Rescues Hippocampus-Dependent Memory Impairment after Acute Hypobaric Hypoxia"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2401-7411","authenticated-orcid":true,"given":"Jiaojiao","family":"Ma","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"},{"name":"School of Medicine, Xiamen University, 361102 Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2829-7750","authenticated-orcid":true,"given":"Miao","family":"Miao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, 210093 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9942-8454","authenticated-orcid":true,"given":"Xiaohong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7256-5111","authenticated-orcid":true,"given":"Xiaohong","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9225-7270","authenticated-orcid":true,"given":"Chenxu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-3677","authenticated-orcid":true,"given":"Yuanzhe","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9972-6051","authenticated-orcid":true,"given":"Chengcheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-3033","authenticated-orcid":true,"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6031-8489","authenticated-orcid":true,"given":"Kangning","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-9175","authenticated-orcid":true,"given":"Chi","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"},{"name":"Shaanxi Provincial Key Laboratory of Bioelectromagnetic Detection and Intelligent Perception, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-2231","authenticated-orcid":true,"given":"Mingming","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, The Air Force Military Medical University, 710032 Xi\u2019an, Shaanxi, China"},{"name":"Shaanxi Provincial Key Laboratory of Bioelectromagnetic Detection and Intelligent Perception, 710032 Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Ma J, Wang C, Sun Y, Pang L, Zhu S, Liu Y, et al. 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