Complete High Thoracic Spinal Cord Injury Causes Bowel Dysfunction in Mice

TL;DR

This study shows that high thoracic spinal cord injury in mice leads to long-term bowel dysfunction, including changes in fecal output and colon motility.

Contribution

The study establishes a new mouse model that replicates human SCI-induced bowel dysfunction for future research.

Findings

SCI mice showed increased fecal pellets in the colon and reduced fecal output compared to sham-injured mice.

SCI caused decreased pellet size and non-significant reductions in colonic motility at multiple timepoints.

SCI led to increased colon muscle contractility and collagen deposition in the distal colon at 21 days post-injury.

Abstract

Bowel dysfunction, is a prevalent and life-impacting comorbidity of spinal cord injury (SCI) with no long-term treatment available. SCI-induced colon changes including motility and fibrosis are understudied as are strategies to address SCI bowel dysfunction. This need remains partly due to the lack of a mouse model that recapitulates the human condition. We hypothesized that a high thoracic spinal transection in mice would trigger bowel dysfunction with coincident colon pathology similar to humans and rats after SCI. We observed bowel dysfunction as increased fecal pellet numbers within the colon, smaller pellet size, and decreased motility. Fecal pellets numbers in the colon increased significantly in SCI animals versus sham (laminectomy only) injuries by 4 days postinjury (dpi) and persisted to 7 and 21 dpi. The number of pellets expelled (fecal output) significantly decreased in SCI versus sham animals at both 7 and 20 dpi. Pellet size was significantly decreased in SCI animals at 7 and 14 dpi, collectively indicative of decreased motility with SCI. SCI caused non-significant reductions in colonic motility (bead expulsion assay) at all three timepoints. Through ex vivo myograph analyses of live colon sections, we detected significant increase in the maximal contractility of the circular musculature from both the proximal and distal colon after SCI at 21 dpi. At the same time point, distal colons displayed significant collagen deposition in the musculature after SCI. Collectively, these findings demonstrate bowel dysfunction immediately after injury that continues in the distal colon over time. Establishing this mouse model enables further interrogation using transgenic models.

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