Paclitaxel-induced astrocytic immunogenic cell death promotes motor function recovery in mice with spinal cord injury

Paclitaxel is a chemotherapy drug widely used in cancer treatment, and in recent years it has been found to have the potential to induce immunogenic cell death (ICD). The purpose of this study was to investigate the role of paclitaxel-induced ICD in scar ablation and neural pathway remodeling after spinal cord injury (SCI). Application of paclitaxel in SCI models resulted in a marked reduction of scar tissue and facilitated axonal passage through the glial scar, thereby promoting neural circuit reconstruction. Subsequent mechanistic investigations revealed a significant upregulation of PERK/eIF2α signaling pathways in astrocytes at the injury site in the treatment group, suggesting that paclitaxel activates ICD in astrocytic, which contributes to glial scar dissolution. Behavioral assessments indicated that recovery of motor function was significantly enhanced in the paclitaxel-treated group compared to the injury-only group. In conclusion, this study elucidates the potential of paclitaxel to facilitate scar resolution and neural circuit reconstruction via the ICD pathway following SCI, offering novel insights and therapeutic strategies for spinal cord repair.