Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (11): 2474-2481.doi: 10.4103/1673-5374.371377

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

Wenxiang Li1, #, Xiaoqing Zhao1, #, Rong Zhang1, #, Xinjie Liu2, Zhangyang Qi1, Yang Zhang1, Weiqi Yang1, Yilin Pang2, Chenxi Zhao1, Baoyou Fan2, Ning Ran1, Jiawei Zhang2, Xiaohong Kong1, Shiqing Feng1, 2, *, Xue Yao1, 2, *   

  1. 1Shandong University Center for Orthopedics, Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China; 2Tianjin Key Laboratory of Spine and Spinal Cord, National Spinal Cord Injury International Cooperation Base, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China
  • Online:2023-11-15 Published:2023-05-05
  • Contact: Xue Yao, PhD, yaoxue@sdu.edu.cn; Shiqing Feng, PhD, shiqingfeng@sdu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81972074 (to XY), the Natural Science Foundation of Tianjin, No. 19JCZDJC34900 (to XY), and National Key Research and Development Project of Stem Cell and Transformation Research, No. 2019YFA0112100 (to SF).

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Abstract: Maintaining the integrity of the blood-spinal cord barrier is critical for the recovery of spinal cord injury. Ferroptosis contributes to the pathogenesis of spinal cord injury. We hypothesized that ferroptosis is involved in disruption of the blood-spinal cord barrier. In this study, we administered the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal cord injury in rats. Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord injury. 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 ferroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Liproxstatin-1 reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Furthermore, inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment. In summary, liproxstatin-1 improved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-spinal cord barrier integrity.

Key words: blood-spinal cord barrier, ferroptosis, liproxstatin-1, neuroinflammation, spinal cord injury, vascular endothelial cells