On Thursday, July 18, 2024 Olivia Wireman successfully defended her dissertation and earned her doctoral degree in physiology. Congratulations, Dr. Wireman!
Characterization of Bowel Dysfunction after Spinal Cord Injury in Mice
Most individuals who suffer a spinal cord injury (SCI) will experience some form of bowel dysfunction. Otherwise known as neurogenic bowel, trauma to the spinal cord can result in severe constipation and/or incontinence. Constipation, specifically, requires extensive bowel routines typically involving the help of another person. Still, many living with SCI are hospitalized due to bowel complications such as fecal impaction. While neurogenic bowel has been well characterized in the clinic, pre-clinical models of neurogenic bowel after SCI are still in development. Most pre-clinical studies in bowel dysfunction after SCI are currently in rats. Studies existing in mice, to our best knowledge, have all been done in low level thoracic injuries (below T8). The highest incidence of constipation is found in humans with high thoracic and cervical level SCI. There remains a significant need to characterize a high-level thoracic SCI model of bowel dysfunction in mice to better mimic the clinical presentation.
For this reason, we have characterized a T3 transection (Tx) mouse model of bowel dysfunction using functional, histological, and molecular assays. We found that mice show acute [4 days post injury (dpi)] and chronic (21 dpi) constipation, measured by fecal output and retention. Specifically, using bead expulsion and ex vivo myography, there is evidence of increased contractility in the distal colon. This increased tone could play a role in the decreased output and increased retention of fecal pellets in animals with a T3 Tx. Molecularly, there was evidence of transient increases in inflammatory cytokine levels within the colon tissue itself. This was followed by an increase of collagen deposition at chronically in the distal colon. Together, acute presence of inflammatory cytokine could dictate the deposition of collagen at chronic timepoints.
We next sought to investigate sex dependent changes in bowel dysfunction. Historically, SCI research has leaned heavily on studies in female mice while the human population of SCI individuals remains predominantly male. Notably, we found a sex dependent response to injury in bowel function as measured by fecal output. Intestinal permeability after injury, however, was unaltered by injury or sex. These standard outcomes of bowel dysfunction had not been extensively investigated in mice up to this point. Thus, we sought to validate these outcomes in a T9 SCI model in mice, commonly used in the SCI research. As expected, the extent of bowel dysfunction was relatively mild in a T9 SCI model compared to T3. Transient changes in fecal output were detected. Interestingly, evidence of collagen deposition was found chronically in the colon tissue. This suggests collagen deposition could be independent of significant constipation. Taken together, these works have characterized a T3 Tx model of bowel dysfunction after SCI using both basic and advanced techniques. It was apparent that foundational techniques, such as fecal output and retention, were sensitive in only the high thoracic transection injury model versus the more commonly used lower-level thoracic contusion model.