Complete High Thoracic Spinal Cord Injury Causes Bowel Dysfunction in Mice.

Area of Science:

• Neuroscience
• Gastroenterology
• Regenerative Medicine

Background:

• Bowel dysfunction is a common and debilitating comorbidity following spinal cord injury (SCI).
• Current treatments for SCI-induced bowel dysfunction are limited, with a lack of effective long-term solutions.
• Understanding the underlying colon pathology and developing suitable animal models are crucial for advancing treatment strategies.

Purpose of the Study:

• To establish and validate a mouse model of high thoracic spinal transection that recapitulates human and rat SCI-induced bowel dysfunction and colon pathology.
• To investigate the temporal changes in colonic motility and structure following SCI in this mouse model.
• To provide a platform for future research into therapeutic interventions for SCI bowel dysfunction.

Main Methods:

• High thoracic spinal transection was performed in mice to induce SCI.
• Bowel function was assessed by quantifying fecal pellet numbers, size, and expulsion.
• Colonic motility was evaluated using a bead expulsion assay and ex vivo myography.
• Colon tissue was analyzed for collagen deposition to assess fibrosis.

Main Results:

• SCI mice exhibited significantly increased fecal pellet numbers in the colon and decreased fecal output compared to sham controls.
• Pellet size was significantly reduced in SCI mice, indicating decreased motility.
• Ex vivo myography revealed increased maximal contractility of colonic musculature 21 days post-SCI.
• Significant collagen deposition was observed in the distal colon of SCI mice at 21 days post-injury.

Conclusions:

• A high thoracic spinal transection mouse model effectively replicates SCI-induced bowel dysfunction and associated colon pathology.
• Bowel dysfunction manifests early after SCI and progresses in the distal colon, involving altered motility and fibrosis.
• This validated mouse model is instrumental for future investigations into the mechanisms and potential treatments for SCI bowel dysfunction.