Mitochondrial-Inflammatory Axis Dysregulation Triggers Disulfidptosis and the Multifaceted Protective Mechanism of Bisphenol A Following Spinal Cord Injury.

Spinal cord injury (SCI) often leads to significant neurological impairment and poses a substantial therapeutic challenge, with disulfidptosis recently identified as a potential mechanism exacerbating such pathologies. This study examined the role of bisphenol A (BPA) in modulating key genes and metabolites associated with disulfidptosis in the context of SCI. Utilizing a murine SCI model, we established three cohorts: a sham control group, an SCI group, and an SCI group treated with BPA. Comprehensive assessments, including locomotor recovery analysis using the Basso Mouse Scale, gait analysis, histopathological evaluations via hematoxylin-eosin and Nissl staining, and integrated transcriptomic and metabolomic profiling, were conducted. BPA administration significantly improved locomotor recovery and mitigated histopathological alterations, with Ndufs1, Ndufa11, and Ndufb10 were identified as pivotal genes and leukotriene B4 and prostaglandin B2 emerged as crucial metabolites. Notably, these genes were intricately linked to the oxidative phosphorylation pathway and exhibited positive intercorrelations, whereas the metabolites were enriched within the arachidonic acid metabolism pathway. As the injury progressed, key gene expression diminished, whereas metabolite concentrations increased. BPA treatment effectively reversed these trends. Collectively, these findings indicate that BPA protects against SCI by disrupting a harmful feedback loop involving mitochondrial dysfunction and inflammatory activation, thus countering disulfidptosis and fostering an environment conducive to neural regeneration, underscoring its potential in SCI management.