Neural Regeneration Research (Jan 2023)

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

  • 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

DOI
https://doi.org/10.4103/1673-5374.371377
Journal volume & issue
Vol. 18, no. 11
pp. 2474 – 2481

Abstract

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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.

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