Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

	Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys
	Zhang, Pei; Chen, Jie-Si; Li, Qi-Ye; Sheng, Long-Xiang; Gao, Yi-Xing; Lu, Bing-Zheng; Zhu, Wen-Bo; Zhan, Xiao-Yu; Li, Yuan; Yuan, Zhi-Bing; Xu, Gang; Qiu, Bi-Tao; Yan, Min; Guo, Chun-Xue; Wang, You-Qiong; Huang, Yi-Jun; Zhang, Jing-Xia; Liu, Fu-Yu; Tang, Zhong-Wei; Ling, Sui-Zhen; Cooper, David N.; Yang, Huan-Ming; Wang, Jian; Gao, Yu-Qi; Yin, Wei; Zhang, Guo-Jie; Yan, Guang-Mei
	2020
发表期刊	ZOOLOGICAL RESEARCH
ISSN	2095-8137
卷号	41 期号:1 页码:3-19
摘要	Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5 alpha-androst-3 beta,5,6 beta-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12730
专题	科研部门_遗传多样性基因组学研究组（张国捷）
推荐引用方式 GB/T 7714	Zhang, Pei,Chen, Jie-Si,Li, Qi-Ye,et al. Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys[J]. ZOOLOGICAL RESEARCH,2020,41(1):3-19.
APA	Zhang, Pei.,Chen, Jie-Si.,Li, Qi-Ye.,Sheng, Long-Xiang.,Gao, Yi-Xing.,...&Yan, Guang-Mei.(2020).Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.ZOOLOGICAL RESEARCH,41(1),3-19.
MLA	Zhang, Pei,et al."Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys".ZOOLOGICAL RESEARCH 41.1(2020):3-19.

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