Postinjury Vagal Nerve Stimulation Protects Against Intestinal Epithelial Barrier Breakdown

Background: Vagal nerve stimulation (VNS) can have a marked anti-inflammatory effect. We have previously shown that preinjury VNS prevented intestinal barrier breakdown and preserved epithelial tight junction protein expression. However, a pretreatment model has little clinical relevance for the care of the trauma patient. Therefore, we postulated that VNS conducted postinjury would also have a similar protective effect on maintaining gut epithelial barrier integrity. Methods: Male balb/c mice were subjected to a 30% total body surface area, full-thickness steam burn followed by right cervical VNS at 15, 30, 60, 90, 120, and 150 minutes postinjury. Intestinal barrier dysfunction was quantified by permeability to 4 kDa fluorescein isothiocyanate-Dextran, histologic evaluation, gut tumor necrosis factor-alpha (TNF-alpha) enzyme-linked immunosorbent assay, and expression of tight junction proteins (myosin light chain kinase, occludin, and ZO-1) using immunoblot and immunoflourescence. Results: Histologic examination documented intestinal villi appearance similar to sham if cervical VNS was performed within 90 minutes of burn insult. VNS done after injury decreased intestinal permeability to fluorescein isothiocyanate-Dextran when VNS was <= 90 minutes after injury. Burn injury caused a marked increase in intestinal TNF-alpha levels. VNS-treated animals had TNF-alpha levels similar to sham when VNS was performed within 90 minutes of injury. Tight junction protein expression was maintained at near sham values if VNS was performed within 90 minutes of burn, whereas expression was significantly altered in burn. Conclusion: Postinjury VNS prevents gut epithelial breakdown when performed within 90 minutes of thermal injury. This could represent a therapeutic window and clinically relevant strategy to prevent systemic inflammatory response distant organ injury after trauma.