Neuroanatomical Remodeling of Colonic Interstitial Cells of Cajal after Spinal Cord Injury.

After spinal cord injury (SCI), individuals often experience gastrointestinal comorbidities including neurogenic bowel, a condition where colonic dysmotility causes chronic constipation, difficulty with evacuation and overflow incontinence. Located intrinsic to the gastrointestinal (GI) tract, the anatomy of the enteric nervous system (ENS) is not directly damaged at the time of the initial spinal trauma, thereby serving as a potential pharmacologic target for neurogenic bowel. Enteric neuromuscular control of colonic slow-wave propagation is a balance of excitatory and inhibitory inputs to Interstitial Cells of Cajal (ICC), pacemaker cells that are interposed between enteric neurons and smooth muscle cells. Reduction of colonic ICCs accompany colonic dysmotility in other disease states and our lab has previously shown a reduction in cholinergic and nitrergic enteric neurons following experimental SCI. Of the ICC subtypes, those of the myenteric plexus are strongly associated with driving colonic motility. We hypothesized that after SCI, the distal colon myenteric plexus ICCs will present with decreased cell bodies and projection length in both sexes, contributing to neurogenic bowel. This study aims to expand current understanding of neurogenic bowel neuroanatomy in acute 3-day and chronic 3-week SCI rats. Experimentally, male and female rats receive a surgical control or severe T3 contusion SCI (n = 19 M, 22 F). Three days or three weeks post-operatively, the distal colon smooth muscle tissue is harvested and dissected for immunohistochemical (IHC) and electrophysiological analysis. C-Kit antibody is then used to fluorescently label the ICCs, upon which we quantified myenteric plexus cell bodies and projection length. Unexpectedly, the myenteric plexus presented with a significant increase in cell count (p = <0.01) and projection length (p = <0.01) following SCI compared to control animals in both sexes. Additionally, a significant interaction effect was observed between animal time point and surgical group for cell count (p = <0.01) and a significant interaction between sex and surgical group for projection length (p = <0.03). The current data illustrates sex-related differences in remodeling of the colonic neuromuscular interface after SCI, reinforcing the importance of sex-specific treatment for neurogenic bowel to improve clinical outcomes. The enduring plasticity of the ICC in our chronic animal model demonstrates the importance of continual medication adjustments among the SCI population. Myenteric ICC network upregulation may reflect a compensatory response to diminished cholinergic enteric neuronal input, therefore our future studies will investigate cholinergic receptor neurophysiology after SCI.