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Abstract

Spinal cord injuries result in the formation of fibrotic scars, which impair tissue regeneration and functional recovery. However, the processes underlying regional differences in the induction and formation of fibrotic scars after spinal cord injury remain unclear. The primary objective of this study was to explore these regional differences and understand how they relate to early functional recovery after spinal cord injury. We found that following the same hemisection injury, the thoracic spinal cord formed the most extensive scar tissue, while the lumbar and cervical regions showed fewer scars. Additionally, these three spinal cord segments showed notable regional differences in early functional recovery after spinal cord injury. Mice with cervical spinal cord injury experienced comparatively swift recovery of hindlimb function, whereas mice with thoracic and lumbar spinal cord injuries showed the poorest hindlimb functional recovery. By comparing the fibrotic scar formation and pro-fibrotic properties of fibroblasts in vitro , we found that fibroblasts in the thoracic regions exhibited the strongest activation, proliferation ability, and pro-fibrotic potential, indicating different mechanistic characteristics of early injury repair. Through a combination of in vivo and in vitro experiments, this study revealed and demonstrated the presence of segmental effects of the spinal cord on fibrotic scar formation and early functional recovery after spinal cord injury. It also addressed the limited understanding of regional heterogeneity in central nervous system scar formation. These findings offer valuable insights for designing region-specific targeted strategies to enhance functional recovery after spinal cord injury.