Single‐Cell Sequencing Reveals the Optimal Time Window for Anti‐Inflammatory Treatment in Spinal Cord Injury

Abstract Though the occurrence of neuroinflammation after spinal cord injury (SCI) is essential for antigen clearance and tissue repair, excessive inflammation results in cell death and axon dieback. The effect of anti‐inflammatory medicine used in clinical treatment remains debatable owing to the inappropriate therapeutic schedule that does not align with the biological process of immune reaction. A better understanding of the immunity process is critical to promote effective anti‐inflammatory therapeutics. However, cellular heterogeneity, which results in complex cellular functions, is a major challenge. This study performs single‐cell RNA sequencing by profiling the tissue proximity to the injury site at different time points after SCI. Depending on the analysis of single‐cell data and histochemistry observation, an appropriate time window for anti‐inflammatory medicine treatment is proposed. This work also verifies the mechanism of typical anti‐inflammatory medicine methylprednisolone sodium succinate (MPSS), which is found attributable to the activation inhibition of cells with pro‐inflammatory phenotype through the downregulation of pathways such as TNF, IL2, and MIF. These pathways can also be provided as targets for anti‐inflammatory treatment. Collectively, this work provides a therapeutic schedule of 1–3 dpi (days post injury) to argue against classical early pulse therapy and provides some pathways for target therapy in the future.