Establishment and multifaceted characterization of a graded spinal cord injury model based on graduated impact depth

Contusion spinal cord injury (SCI) models are extensively used in preclinical research because of their ability to mimic the pathophysiological characteristics observed in humans. Although various impact devices have been developed to establish graded contusion SCI models, few studies have systematically investigated the relationship between impact depth and injury severity. In this study, we aimed to establish and characterize a graded SCI model, with impact depth as the independent variable.

A precise impactor system was used to establish graded SCI models by adjusting the impact depth, with comprehensive evaluations of locomotor function, imaging, histology, and transcriptomic profiles of the injured spinal cord. Additionally, gene expression trend analysis and subsequent Gene Ontology enrichment analysis were performed to investigate the potential biological mechanisms associated with injury severity.

The Basso, Beattie, Bresnahan (BBB) score and CatWalk gait analysis demonstrated a severity-dependent functional recovery pattern in different impact depth groups across multiple postinjury time points. Magnetic resonance imaging and histological results revealed a correlation between impact depth and lesion size. Principal component analysis and heat map clustering of the transcriptomic profile revealed intragroup clustering and intergroup separation, with different injury severities across different time points postinjury. Furthermore, biological mechanisms that correlated with injury severity were identified using gene expression trend analysis.

This study established a quantifiable, graded rat SCI model that was comprehensively evaluated using multiple approaches and may serve as a valuable platform for future SCI research.