Single-cell sequencing reveals the optimal time window for anti-inflammatory treatment in spinal cord injury

Abstract

Abstract Neuroinflammation is a necessary response to spinal cord injury (SCI) as it helps to clear antigens and promote tissue repair. However, excessive inflammation can result in the death of cells and axon dieback. The efficacy of anti-inflammatory medication in clinical treatment is still up for debate due to inappropriate therapeutic scheduling that does not align with the biological process of immune response. A better understanding of the immune process is crucial for effective anti-inflammatory therapeutics, but it is challenged by cellular heterogeneity and complex cellular functions. To address this, we conducted a single-cell RNA sequencing study and profiled tissue proximity to the injury site at various time points after SCI. Based on our analysis of single-cell data and histochemistry observations, we recommend an appropriate time window of 1-3 days post-injury for anti-inflammatory medication treatment. We also verified the mechanism of MPSS, a typical anti-inflammatory medication, which was found to inhibit the activation of cells with pro-inflammatory phenotypes by downregulating pathways such as TNF, IL2, and MIF. These pathways could be potential targets for anti-inflammatory treatment. In summary, we recommend a therapeutic schedule of 1-3 days post-injury to argue against classical early pulse therapy and provide potential pathways for target therapy in the future.