Bowel dysfunction, in the form of constipation and/or incontinence, is one of the most prevalent and life-impacting co-morbidities associated with spinal cord injury (SCI) with no long- term treatment available. The extent to which SCI-induced changes in the colon (e.g. inflammation, fibrosis, and reduced enteric neuron density) cause progressive dysfunction is understudied. There remains a significant unmet need to develop strategies to prevent or reverse bowel dysfunction after SCI. This need remains, in part, due to the lack of a mouse model which recapitulates the human condition. We hypothesized that a T3 spinal transection in mice would trigger bowel dysfunction alongside early colonic inflammation and downstream remodeling of the colon musculature as seen in both humans and rats after SCI. Bowel dysfunction was defined as increased number of fecal pellets within the colon, smaller pellet size, and decreased water content in the stool. The number of fecal pellets within the colon increased significantly in animals receiving SCI compared to sham (laminectomy only) injuries by 4 days post injury (dpi) and persisted to 21dpi. Furthermore, fecal pellet size was significantly decreased in the SCI animals at 21dpi and trended toward decreased water content. Together, these functional measurements are indicative of chronic bowel dysfunction after T3 transection. We next molecularly interrogated whole colon tissue for inflammatory cytokine levels and found increased levels of IFN-γ at 4 dpi but not at 21dpi and found increased collagen deposition in the colonic musculature at both 4 and 21 dpi in the SCI versus sham animals. The acute spike in INF-γ and deposition of collagen after injury are consistent with our hypothesis that T3 transection causes acute inflammation followed by remodeling of the colon wall. Establishing this mouse model will enable further interrogation of cell-type specific responses and signaling pathways using transgenic models. T32 Fellowship in Physiology (GM118292) and T32 Fellowship Neurobiology of CNS Injury & Repair (5T32 NS077889) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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