Histopathological Changes in the Colon Accompany Dysmotility Following Experimental Spinal Cord Injury
Authors: White Amanda R , Cooper Timothy K , Holmes Gregory M 
Published: November 2023

Colonic dysregulation is a common co‐morbidity of spinal cord injury (SCI) for over 285,000 Americans living with SCI. Diminished colonic transit, constipation, evacuation dyssynergy, and overflow incontinence are widely acknowledged as lifelong physical and psychological challenges gravely impacting quality of life. Despite the enormity of the problem, significant knowledge gaps persist regarding the mechanisms and changes leading to colonic dysregulation after SCI. Gastrointestinal morphology can change due to diet, age, stress, and/or disease. Mucosal crypt depth and thickness of the muscularis propria are indicators of intestinal health and morphological alterations of these structures accompany functional bowel disorders. The histopathological and functional changes that occur within the post‐SCI colon remain obscure, but studies of chronic inflammatory bowel diseases suggest that the morphological and pathophysiological changes associated with inflammation provoke colonic remodeling and dysmotility.

Aim

We hypothesized that SCI induces abnormal changes within the colonic mucosa and muscular compartment; thereby contributing to colonic dysregulation.

Methods

Male Wistar rats received a T3 contusion SCI at 3 days and 3 weeks prior to in vivo experimentation and tissue harvest for histological evaluation. In vivo proximal and distal colonic contractility were simultaneously quantified by sub‐miniature pressure transducers. Whole tissue colonic samples from SCI or surgical controls were processed and analyzed via H&E and Masson's trichrome histological stains. Slides were blindly scored for inflammatory or structural changes within the colonic mucosa as well as thickness and collagen content of the muscularis propria.

Results

Extending our previous findings, contractions within the proximal and distal colon were significantly reduced 3‐days after SCI and persisted in 3‐week SCI rats. Colonic mucosal crypt depth and width was significantly reduced within the proximal colon of both 3‐day and 3‐week SCI rats. Conversely, the distal colon only demonstrated significant changes in crypts in 3‐week SCI rats. Muscularis propria thickness of the proximal colon was significantly increased only in the 3‐week SCI rats, but the distal colon demonstrated a significant muscularis propria thickness in both 3‐day and 3‐week SCI rats. Collagen content within the muscularis propria of both the ascending and descending colon was significantly increased in both the 3‐day and 3‐week SCI rats.

Conclusion

The diminished depth and width of mucosal crypts and increased muscle thickness and collagen content suggests possible progressive changes that contribute to diminished bowel function following T3‐SCI. Derangements in collagen networks and shortening of mucosal crypts are hallmarks of animals with colitis, and contribute to the observed bowel motor dysfunctions. Our data suggests that T3‐SCI may induce morphological changes within the colon, similar to those seen in inflammatory bowel diseases, which affect the normal physiology and contribute to long‐term colonic dysmotility.

Support or Funding Information

NINDS #049177