ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1662389
This article is part of the Research TopicModel Organisms in Neuropharmacology 2024View all 4 articles
Tetramethylpyrazine exerts neuroprotective effects in a mouse model of acute hypobaric hypoxia
Provisionally accepted
Xiong Lan1,2
Wei Zhou2Lei Zhou2
Huifang Deng2
Pan Shen2Zhijie Bai2
Chaoji Huangfu2
Ningning Wang2Yue Sun2Chengrong Xiao2
Ma Zengchun2
Pengfei Zhang2*
Yue Gao1,2*- 1Guangdong Pharmaceutical University, Guangzhou, China
- 2Beijing Institute of Radiation Medicine, Beijing, China
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Cognitive impairment is prevalent among individuals ascending to high-altitude regions, yet effective preventive or therapeutic medications remain lacking. Tetramethylpyrazine (TMP), a small-molecule agent, demonstrates blood-brain barrier permeability and exhibits neuroprotective properties in multiple neurological disorders. Here we find TMP exhibits neuroprotective effects against hypoxia-induced damage using a simulated high-altitude hypoxia model. Specifically, TMP prolongs survival, alleviates cognitive impairment, elevates cerebral ATP levels and alleviates hippocampal cellular edema in hypobaric hypoxic mice. TMP also reduces hypoxia-induced neuronal death in vitro. Mechanistic investigations identify that TMP potentially binds to the ion channel protein KCNK2 (potassium two pore domain channel subfamily K member 2, also known as TREK-1), and inhibits TREK-1-mediated current in vitro. These findings demonstrate that TMP is neuroprotective under hypobaric hypoxia and represents a potential therapeutic candidate for alleviating high-altitude-induced cognitive dysfunction.
Keywords: hypobaric hypoxia, Tetramethylpyrazine, neuroprotective, cognitive dysfunction, TREK-
Received: 09 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Lan, Zhou, Zhou, Deng, Shen, Bai, Huangfu, Wang, Sun, Xiao, Zengchun, Zhang and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Pengfei Zhang, sdyxyzpf@163.com
Yue Gao, gaoyue@bmi.ac.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.