Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury  

作　　者：Wenxing Cui Xun Wu Dayun Feng Jianing Luo Yingwu Shi Wei Guo Haixiao Liu Qiang Wang Liang Wang Shunnan Ge Yan Qu 

机构地区：[1]Department of Neurosurgery,Tangdu Hospital,Fourth Military Medical University,Xi’an,710038,China

出　　处：《Neuroscience Bulletin》2021年第8期1160-1175,共16页神经科学通报（英文版）

基　　金：the National Natural Science Foundation of China(81630027).

摘　　要：Traumatic brain injury(TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes,but the pathogenesis remains poorly understood.In this study,we aimed to investigate the causal role of acrolein,a typical lipid peroxidation product,in TBI-induced coagulopathy,and further explore the underlying molecular mechanisms.We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy.Using a controlled cortical impact mouse model,we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor(VWF).Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion.mRNA sequencing(mRNA-seq)and transcriptome analysis indicated that acrolein over-activated autophagy,and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway.In addition,we demonstrated that acrolein was produced in the perilesional cortex,affected endothelial cell integrity,and disrupted the blood-brain barrier.In conclusion,in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage,providing an alternative therapeutic target.

关 键 词：Traumatic brain injury COAGULOPATHY AUTOPHAGY ACROLEIN Von Willebrand factor 

分 类 号：R285.5[医药卫生—中药学]