Efferent vagal nerve stimulation attenuates gut barrier injury after burn: Modulation of intestinal occludin expression

Introduction: Severe injury can cause intestinal permeability through decreased expression of tight junction proteins, resulting in systemic inflammation. Activation of the parasympathetic nervous system after shock through vagal nerve stimulation is known to have potent anti-inflammatory effects; however, its effects on modulating intestinal barrier function are not fully understood. We postulated that vagal nerve stimulation improves intestinal barrier integrity after severe burn through an efferent signaling pathway, and is associated with improved expression and localization of the intestinal tight junction protein occludin. Methods: Male balb/c mice underwent right cervical vagal nerve stimulation for 10 minutes immediately before 30% total body surface area, full-thickness steam burn. In a separate arm, animals underwent abdominal vagotomy at the gastroesophageal junction before vagal nerve stimulation and burn. Intestinal barrier injury was assessed by permeability to 4 kDa FITC-dextran, histology, and changes in occludin expression using immunoblotting and confocal microscopy. Results: Cervical vagal nerve stimulation decreased burn-induced intestinal permeability to FITC-dextran, returning intestinal permeability to sham levels. Vagal nerve stimulation before burn also improved gut histology and prevented burn-induced changes in occludin protein expression and localization. Abdominal vagotomy abrogated the protective effects of cervical vagal nerve stimulation before burn, resulting in gut permeability, histology, and occludin protein expression similar to burn alone. Conclusion: Vagal nerve stimulation performed before injury improves intestinal barrier integrity after severe burn through an efferent signaling pathway and is associated with improved tight junction protein expression.