Protective mechanism of zinc ions in spinal cord injury treatment: regulation of mitochondrial function and reduction of apoptosis via TNF-α pathway inhibition.

Spinal cord injury (SCI) profoundly impacts quality of life and involves complex pathologies like inflammation, oxidative stress, and metabolic dysregulation. The tumor necrosis factor (TNF) signaling pathway is crucial in SCI-related inflammation, affecting injury progression and recovery. Our study investigates the potential role of zinc ions in SCI treatment, particularly focusing on the TNF signaling pathway. Bulk RNA-seq analysis of SCI mice at various time points revealed significant trends in apoptotic and mitochondrial protein changes. Gene enrichment analysis post‑zinc treatment indicated its primary effects on inflammation and apoptosis pathways, with protective actions likely mediated through modulation of the TNF-α signaling pathway. Further in vivo and in vitro experiments confirmed that zinc ions alleviate TNF-α-mediated pyroptosis and oxidative stress, and protect mitochondrial function. These findings offer new insights into SCI treatment, elucidating the interaction between zinc ions and the TNF signaling pathway, thus providing a theoretical basis for improving patient outcomes and quality of life.