Ferroptosis inhibition protects vascular endothelial cells and maintains integrity of the blood-spinal cord barrier after spinal cord injury

作     者：Wenxiang Li Xiaoqing Zhao Rong Zhang Xinjie Liu Zhangyang Qi Yang Zhang Weiqi Yang Yilin Pang Chenxi Zhao Baoyou Fan Ning Ran Jiawei Zhang Xiaohong Kong Shiqing Feng Xue Yao Wenxiang Li;Xiaoqing Zhao;Rong Zhang;Xinjie Liu;Zhangyang Qi;Yang Zhang;Weiqi Yang;Yilin Pang;Chenxi Zhao;Baoyou Fan;Ning Ran;Jiawei Zhang;Xiaohong Kong;Shiqing Feng;Xue Yao

作者机构：Shandong University Center for OrthopedicsDepartment of OrthopedicsQilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Tianjin Key Laboratory of Spine and Spinal CordNational Spinal Cord Injury International Cooperation BaseDepartment of OrthopedicsTianjin Medical University General HospitalTianjinChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第11期

页      面：2474-2481页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：National Natural Science Foundation of China,No.81972074 (to XY) Natural Science Foundation of Tianjin,No.19JCZDJC34900 (to XY) National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100 (to SF)。 

主　　题：blood-spinal cord barrier ferroptosis liproxstatin-1 neuroinflammation spinal cord injury vascular endothelial cells 

摘      要：Maintaining the integrity of the blood-spinal cord barrier is critical for the recove ry of spinal cord injury.Ferro ptosis contributes to the pathogenesis of spinal cord injury.We hypothesized that ferroptosis is involved in disruption of the blood-s pinal cord barrier.In this study,we administe red the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal co rd injury in rats.Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord inju ry.Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein.Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury,as shown by the immunofluorescence of an endothelial cell marker(rat endothelium cell antigen-1,RECA-1) and fe rroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase.Liproxstatin-1reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member4 and 15-lipoxygenase.Furthermore,inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment.In summary,liproxstatin-1im proved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-s pinal co rd barrier integrity.