Small-bowel obstruction impairs epithelial barrier function and is associated with persistent NOS2 suppression and sustained brainstem activation.

BACKGROUND

Mechanical small-bowel obstruction impairs epithelial barrier function and engages neuroimmune signaling along the gut-brain axis. We hypothesized that obstruction release would restore intestinal barrier function, ileal inflammatory gene expression, and neuroimmune signaling in the nucleus tractus solitarius.

METHODS

Small-bowel obstruction was induced in mice by ileal ligation for 3 or 9 hours, with a subgroup undergoing ligation release after 3 hours, followed by a 3-hour recovery. Time-matched sham-operated animals served as controls. Intestinal permeability was quantified by measuring fluorescein ex vivo in Ussing chambers. Ileal messenger RNA expression of inducible nitric oxide synthase, tumor necrosis factor α, and cyclooxygenase-2 was quantified by quantitative real-time polymerase chain reaction. Nucleus tractus solitarius neuronal activation was assessed by c-Fos expression in brainstem sections by immunohistochemistry.

RESULTS

Intestinal fluorescein permeability differed between groups (Kruskal-Wallis P = 4.0 × 10-5), with higher permeability during small-bowel obstruction and this effect largely normalized after obstruction release. Despite this early barrier improvement, nucleus tractus solitarius c-Fos activation persisted after release. Ileal inducible nitric oxide synthase expression was markedly suppressed during obstruction (0.06-fold from control, Holm-adjusted P = .010, versus time-matched sham) and remained lower after release (0.03-fold from control, Holm-adjusted P = .062), although this difference did not reach statistical significance after correction, whereas tumor necrosis factor α and cyclooxygenase-2 levels showed no significant changes at the sampled time points.

CONCLUSION

Small-bowel obstruction rapidly impairs epithelial barrier function and elicits sustained nucleus tractus solitarius activation beyond obstruction release. Sustained reduction of inducible nitric oxide synthase messenger RNA persists despite early ex vivo barrier improvement. These findings point to distinct epithelial, neuronal, and immune trajectories during obstruction and early recovery.