Single-cell sequencing for the molecular identity involved in zinc therapy for spinal cord injury

Spinal cord injury (SCI) is a severe traumatic neurological condition often caused by car accidents, violent impacts, or unintentional falls and can have devastating consequences for the patient. SCI include primary and secondary injuries. Followed by primary injury, and secondary injuries including inflammatory responses and oxidative stress, which exacerbate the disease process of SCI. Therefore, the treatment of SCI, especially the suppression of secondary injuries, is a major focus of attention in the field of neuroscience. In previous studies, we have demonstrated that zinc therapy can exert neuroprotective effects in mice after acute SCI, including reducing the inflammatory response in the central nervous system, decreasing the neuronal apoptosis and downregulating oxidative stress at the region of injury. However, little is known about how zinc therapy systematically alleviates SCI. Here, we have systematically analysed and mapped the single-cell atlas of the spinal cord in mice with SCI treated by zinc therapy, which provides a systematic analysis of the transcriptome of individual cells in the spinal cord. Among the results, we found that zinc therapy-induced alterations in the IL-17 inflammatory pathway and produced immune heterogeneity in microglia which are the inherent immune cells in the central nervous system. By cell subpopulations clustering analysis, we defined seven microglia subpopulations in zinc-therapy spinal cord tissue and identified the presence of novel VEGFA+ microglia. This finding presents that the microglia subpopulations affected by zinc therapy may have the potential to promote angiogenesis, which is a potential mechanism for the treatment of SCI. In conclusion, this study maps/reveals the transcriptomic of zinc therapy for the treatment of acute SCI with unprecedented resolution and provides a molecular basis for the clinical application.