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作 者:Yao Jing Dian-Xu Yang Wei Wang Fang Yuan Hao Chen Jun Ding Zhi Geng Heng-Li Tian
机构地区:[1]Department of Neurosurgery,Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai 200233,China [2]Department of Neurology,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai 200233,China
出 处:《Neuroscience Bulletin》2020年第6期625-638,共14页神经科学通报(英文版)
基 金:supported by the National Natural Science Foundation of China (81671207,81701895,and 81501048);the Shanghai Jiao Tong University Medicine-Engineering Research Fund (YG2016QN20).
摘 要:Aloin is a small-molecule drug well known for its protective actions in various models of damage.Traumatic brain injury(TBI)-induced cerebral edema from secondary damage caused by disruption of the blood-brain barrier(BBB) often leads to an adverse prognosis.Since the role of aloin in maintaining the integrity of the BBB after TBI remains unclear,we explored the protective effects of aloin on the BBB using in vivo and in vitro TBI models.Adult male C57 BL/6 mice underwent controlled cortical impact injury,and mouse brain capillary endothelial bEnd.3 cells underwent biaxial stretch injury,then both received aloin treatment.In the animal experiments,we found 20 mg/kg aloin to be the optimum concentration to decrease cerebral edema,decrease disruption of the BBB,and improve neurobehavioral performance after cortical impact injury.In the cellular studies,the optimum concentration of 40 μg/mL aloin reduced apoptosis and reversed the loss of tight junctions by reducing the reactive oxygen species levels and changes in mitochondrial membrane potential after stretch injury.The mechanisms may be that aloin downregulates the phosphorylation of p38 mitogen-activated protein kinase,the activation of p65 nuclear factor-kappa B,and the ratios of B cell lymphoma(Bcl)-2-associated X protein/Bcl-2 and cleaved caspase-3/caspase-3.We conclude that aloin exhibits these protective effects on the BBB after TBI through its anti-oxidative stress and anti-apoptotic properties in mouse brain capillary endothelial cells.Aloin may thus be a promising therapeutic drug for TBI.
关 键 词:ALOIN Blood-brain barrier Traumatic brain injury Oxidative stress APOPTOSIS
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