title: Postinjury vagal nerve stimulation protects against intestinal epithelial barrier breakdown.
abstract: 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-α) 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-α levels. VNS-treated animals had TNF-α 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.
  
  
  CONCLUSIONS
  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.
authors: Division of Trauma, Surgical Critical Care, and Burns, Department of Surgery, University of California, San Diego School of Medicine, San Diego, California 92103-8896, USA.
authors: Michael
authors: M
authors: Krzyzaniak
authors: Carrie
authors: C
authors: Peterson
authors: William
authors: W
authors: Loomis
authors: Ann-Marie
authors: AM
authors: Hageny
authors: Paul
authors: P
authors: Wolf
authors: Luiz
authors: L
authors: Reys
authors: James
authors: J
authors: Putnam
authors: Brian
authors: B
authors: Eliceiri
authors: Andrew
authors: A
authors: Baird
authors: Vishal
authors: V
authors: Bansal
authors: Raul
authors: R
authors: Coimbra
references: J Neurotrauma. 2009 Aug;26(8):1353-9
references: 19344293
references: J Trauma. 2010 Jun;68(6):1349-54; discussion 1354-6
references: 20539179
references: Curr Gastroenterol Rep. 1999 Oct;1(5):410-6
references: 10980980
references: Am J Physiol. 1987 Dec;253(6 Pt 1):C854-61
references: 3425707
references: Curr Opin Crit Care. 2001 Apr;7(2):92-8
references: 11373517
references: Burns. 2010 Feb;36(1):75-81
references: 19646819
references: J Trauma. 1968 Nov;8(6):1049-51
references: 5722120
references: Am J Pathol. 2006 Dec;169(6):1901-9
references: 17148655
references: Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G496-504
references: 16474009
references: Nature. 2003 Jan 23;421(6921):384-8
references: 12508119
references: World J Surg. 1996 May;20(4):411-7
references: 8662128
references: Nature. 2000 May 25;405(6785):458-62
references: 10839541
references: Am J Physiol Gastrointest Liver Physiol. 2010 Dec;299(6):G1308-18
references: 20705905
references: J Exp Med. 2006 Jul 10;203(7):1623-8
references: 16785311
references: Pediatr Dev Pathol. 1998 Jan-Feb;1(1):2-16
references: 10463267
references: Shock. 2009 Apr;31(4):416-22
references: 18791495
references: J Cell Sci. 2006 May 15;119(Pt 10):2095-106
references: 16638813
references: J Trauma. 2009 Jan;66(1):17-24; discussion 24-5
references: 19131801