神经炎症
莫里斯水上航行任务
药理学
虫草素
神经保护
TLR4型
缺氧(环境)
血脑屏障
埃文斯蓝
医学
化学
海马体
内科学
炎症
中枢神经系统
生物化学
有机化学
氧气
作者
Pengfei Liu,Lei Pan,Lei Cui,Tianzuo Li,S. J. Zhao,Yuxin Hu,Xiaomei Tao,Hui Deng,Jingwen Jiang,Bin-Jiang Zhao,Yong Wang,Xinying Xue
标识
DOI:10.1016/j.ejphar.2022.174952
摘要
Hypobaric hypoxia exposure leads to brain edema, followed by neuropsychological disorders. However, the related mechanism and effective treatments are still unclear. The study aimed to discuss the neuroprotective effects of Cordycepin on hypobaric hypoxia-induced cognitive impairment.The study contained two parts. In the first part, rats underwent hypobaric hypoxia (HH) exposure for 7 days, with or without Cordycepin (10 mg/kg) or lipopolysaccharide (LPS,10 mg/kg) treatment once a day. In the second part, rats underwent HH exposure for 7 days, with or without TAK242 (3 mg/kg) and Cordycepin (10 mg/kg) once a day. Open field and Morris water maze test were performed one day after the 7days treatment. The BBB permeability was detected by the uptake of NaF. Western bloting was used to detect the levels of TLR4/MyD88/NF-κB pathway related proteins in the hippocampus. The hippocampal and serous levels of cytokines were detected by ELISA. The structure of tight junctions in the hippocampus was observed under the transmission electron microscopy.Both acute HH and LPS exposure could activate the TLR4 pathway and neuroinflammation, further induced BBB disruption and cognitive injury. Cordycepin could inhibit the activation of theTLR-4/NF-κB/MMP-9 pathway, which further attenuated cognitive dysfunction, and disruption of the blood-brain barrier (BBB) in HH and LPS exposed rats. Furthermore, TAK242, a TLR4 antagonist, also inhibited the activation of theTLR-4/NF-κB/MMP-9 pathway and BBB disruption, as well as attenuated HH induced cognitive impairment.Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway.
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