Establishing an experimental model approach to thermal-induced spinal cord injury in mice.

Abstract

Neurological deficits following spinal surgery represent a severe complication, and thermal damage from high-speed drills is considered a potential cause, but the underlying pathophysiology remains poorly understood. Here, we aimed to develop and characterize a novel mouse model of thermal-induced spinal cord injury (TiSCI). Given that surgical drilling can generate temperatures of 90 °C, we created a TiSCI model by applying a controlled thermal exposure (90 °C for 1 min) to the exposed thoracic cord in mice. The TiSCI model induced significant and persistent hindlimb motor deficits, accompanied by marked demyelination and progressive collagen deposition at the lesion site. Transcriptomic analysis by RNA-sequencing revealed that this pathology was associated with a significant upregulation of pro-fibrotic genes, including Col1a1, Col1a2, Tgfβ1, and Acta2. Using Col1a2-EGFP transgenic mice, we identified a prominent fibrotic scar composed of Type I collagen-producing cells at the lesion site, evident by 7 and 14 days post-injury, which spatially overlapped with demyelinated regions devoid of axons. KEGG pathway analysis highlighted pathways related to extracellular matrix organization, phagocytosis, and fibroblast activation. Notably, Scarb3 and Actg2 were upregulated early, while Itgax and Fzd7 were induced later, implicating both immune cell responses and Wnt/β-catenin signaling in fibrotic scar progression. In conclusion, this study established an experimental platform for investigating TiSCI in mice, providing first direct evidence that a thermal insult causes persistent neurological deficits by inducing a robust fibrotic response. The resulting collagenous scar acts as a physical barrier to axonal connectivity, establishing the fibrotic process as a key therapeutic target.