A survival model of thoracic contusion spinal cord injury in the domestic pig

Abstract

Spinal cord injury (SCI) frequently results in motor, sensory and autonomic dysfunction for which there is currently no cure. Recent preclinical and clinical research has led to promising advances in treatment; however, therapeutics indicating promise in rodents have not translated successfully in human trials, likely due, in part, to gross anatomical and physiological differences between the species. Therefore, large animal models of SCI may facilitate the study of secondary injury processes that are influenced by scale, and assist the translation of potential therapeutic interventions. The aim of this study was to characterize two severities of thoracic contusion SCI in female domestic pigs, measuring motor function and spinal cord lesion characteristics, over two weeks post-SCI. A custom instrumented weight drop injury device was used to release a 50 g impactor from 10 cm (n=3) or 20 cm (n=7) onto the exposed dura, to induce a contusion at the T10 thoracic spinal level. Hind limb motor function was assessed at 8 and 13 days post-SCI using a 10-point scale. Volume and extent of lesion-associated signal hyperintensity in T2-weighted magnetic resonance (MR) images was assessed at 3, 7 and 14 days post-injury. Animals were transcardially perfused at 14 days post-SCI and spinal cord tissue was harvested for histological analysis. Bowel function was retained in all animals and transient urinary retention occurred in one animal after catheter removal. All animals displayed hind limb motor deficits. Animals in the 10 cm group demonstrated some stepping and weight bearing and scored a median 2- 3 points higher on the 10-point motor function scale at 8 and 13 days post-SCI, than the 20 cm group. Histological lesion volume was 20 % greater, and 30 % less white matter was spared, in the 20 cm group than in the 10 cm group. The MR signal hyperintensity in the 20 cm injury group had a median cranial-caudal extent approximately 1.5 times greater than the 10 cm injury group at all three time points, and median volumes 1.8, 2.5 and 4.5 times greater at day 3, 7 and 14 post-injury, respectively. Regional differences in axonal injury were observed between groups, with amyloid precursor protein immunoreactivity greatest in the 20 cm group in spinal cord sections adjacent the injury epicenter. This study demonstrated graded injuries in a domestic pig strain, with outcome measures comparable to miniature pig models of contusion SCI. The model provides a vehicle for the study of SCI and potential treatments, particularly where miniature pig strains are not available and/or where small animal models are not appropriate for the research question.