Pengfei Liu1, Lei Pan2, Lei Cui3, Tianzuo Li4, Sheng Zhao5, Yanting Hu4, Xiaomei Tao6, Hui Deng7, Jingwen Jiang4, Binjiang Zhao8, Yong Wang9, Xinying Xue10. 1. Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. Electronic address: sfflpf@126.com. 2. Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. Electronic address: leipan61@aliyun.com. 3. Department of Plastic Surgery, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. Electronic address: cuileite@aliyun.com. 4. Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. 5. Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100037, China. 6. Department of Pharmacy and Pharmacology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China. 7. Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. 8. Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. Electronic address: zhaobinjiang@sina.com. 9. Vice President for the Emergency Services, Beijing Emergency Medical Center, No.103 Qianmen West Street, Xicheng District, Beijing, China. Electronic address: wangyon97096@aliyun.com. 10. Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Beijing, 100038, China. Electronic address: xinyingxue2010@163.com.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway.