Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.

Autor: Ma YY; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Li X; Army 953 Hospital, Shigatse Branch of Xinqiao Hospital, Third Military Medical University, Shigatse, 857000, China., Yu ZY; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Luo T; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China., Tan CR; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Bai YD; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Xu G; Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, China.; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, 400038, China.; Key Laboratory of High Altitude and Frigidzone Medical Support, PLA, Chongqing, 400038, China., Sun BD; Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, China.; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, 400038, China.; Key Laboratory of High Altitude and Frigidzone Medical Support, PLA, Chongqing, 400038, China., Bu XL; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Liu YH; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Jin WS; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China., Gao YQ; Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, 400038, China.; Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, 400038, China.; Key Laboratory of High Altitude and Frigidzone Medical Support, PLA, Chongqing, 400038, China., Zhou XF; Suzhou Auzone Biotech, Suzhou, 215123, China.; Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia., Liu J; Department of Special Medicine, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. liujuan961@163.com.; Center for Hyperbaric Oxygen Medicine, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. liujuan961@163.com., Wang YJ; Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.; Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.; State Key Laboratory of Trauma and Chemical Poisoning, Chongqing, 400042, China. yanjiang_wang@tmmu.edu.cn.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2024 Oct 03; Vol. 14 (1), pp. 415. Date of Electronic Publication: 2024 Oct 03.
DOI: 10.1038/s41398-024-03133-1
Abstrakt: Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.
(© 2024. The Author(s).)
Databáze: MEDLINE
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