61 - Paracellular Flux After Spinal Cord Injury Is Nonuniform Along the Gastrointestinal Tract

Poster Board Number: 61
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Abstract Body : Following spinal cord injury (SCI), many individuals develop systemic inflammatory response syndrome (SIRS), a life-threatening condition. While understanding of the mechanisms that lead to SIRS following SCI is incomplete, clinical and preclinical evidence have implicated gastrointestinal (GI) epithelial barrier compromise and associated bacterial translocation. In a physiologic state, the GI epithelial tight junction (TJ) barrier excludes luminal antigens. Disruption of the TJ barrier increases permeability of antigens, leading to inflammation. Previous work has demonstrated an increase in GI barrier permeability following SCI using an orally administered tracer, however, these results did not specify segmental permeability of the GI tract. We aim to investigate if post-SCI GI barrier compromise develops uniformly in the foregut, midgut, and hindgut. Following SCI, the GI tract experiences hypoperfusion, with superior and inferior mesenteric arteries particularly affected. We hypothesize that after SCI, the colon is the primary site of GI epithelial barrier breakdown.

This study aims to investigate differential responses in barrier permeability post-SCI along the GI tract. Male Wistar rats were administered a T3 spinal compression/contusion injury, or surgical control procedure. The GI tract was harvested 3 days after surgery, and full-thickness tissue from the duodenum, proximal colon, and distal colon was mounted in Ussing chambers to measure barrier permeability ex-vivo (duodenum, n=9; proximal colon, n=12; distal colon, n=6). Radiolabeled molecules of differing size ([14C]urea, 60g/mol; [3H]inulin, 5000g/mol) were used to probe permeability of the paracellular pathway. Both tracer molecules were introduced to the apical chamber simultaneously, allowed to equilibrate for 5 minutes, and then basal solution samples were taken over the course of 1 hour. Sample radioactivity was then quantified with a scintillation counter, from which average molar flux of the tracers was calculated. In the duodenum, urea (p= < 0.01) and inulin (p= < 0.05) flux were elevated in the SCI group compared to control. In the proximal colon, only urea flux was elevated following SCI compared to control (p= < 0.05). There were no significant differences between SCI and control animal distal colon tissue. This data indicates that barrier disruption develops nonuniformly along the GI tract following SCI. At day 3 post-SCI, duodenum was significantly more permeable to both urea and inulin probes. This represents an increase in flux through both canonical TJ paracellular pathways: the pore (small molecule) and leak (large molecule) pathway. These findings suggest that the duodenum plays a larger role in post-SCI GI barrier pathophysiology than has been previously reported, providing a new target for investigating the causes underlying post-SCI systemic inflammation. Future studies will investigate structural changes underlying these findings, characterizing TJ protein composition and the time course of TJ barrier disruption following SCI.