• Ruizhang Yao, Mo Liu, Fang Liang, Zhencheng Sun, Jing Yang, Junlin Zhou, Qingjun Su, and Xuehua Liu.
• Department of Orthopedic Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
• Spine. 2023 Nov 15; 48 (22): 155315601553-1560.

Study DesignBasic science study investigating the potential molecular mechanisms of hyperbaric oxygen (HBO) therapy in mice with spinal cord injury (SCI).ObjectiveWe aimed to explore the intrinsic mechanisms of HBO for SCI through the lens of ferroptosis in the subacute phase.Summary Of Background DataHBO has been observed to facilitate the restoration of neurological function subsequent to SCI. Ferroptosis is a distinct cellular death mechanism that can be distinguished from apoptosis, necrosis, and autophagy. However, the precise relationship between these two phenomena remains poorly understood.MethodsWe established an SCI model and employed a range of techniques, including behavioral assessments, electron microscopy, immunofluorescence, RT-qPCR, Western blotting (WB), Glutathione (GSH) measurement, and iron assay, to investigate various aspects of HBO therapy on SCI in mice. These included analyzing mitochondrial morphology, neuronal count, GSH levels, iron levels, and the expression of genes (Acyl-CoA synthetase family member-2, Iron-responsive element-binding protein-2) and proteins (Glutathione peroxidase 4; system Xc-light chain) associated with ferroptosis. The study included three groups: Sham-operated, SCI, and HBO. Group comparisons were performed using one-way analysis of variance and one-way repeated measures analysis of variance, followed by Tukey's post hoc test. Statistical significance was set at a P < 0.05.ResultsOur findings revealed that HBO therapy significantly enhanced the recovery of lower limb motor function in mice following SCI in the subacute phase. This was accompanied by upregulated expression of GPX4 and system Xc-light chain proteins, elevated GSH levels, increased number of NeuN+ cells, decreased expression of the iron-responsive element-binding protein-2 gene, and reduced iron concentration.ConclusionsOur research suggests that HBO therapy has the potential to be an effective treatment for SCI in the subacute phase by mitigating ferroptosis.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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