title: Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury.
abstract: BACKGROUND
  Traumatic brain injury (TBI) causes gastrointestinal dysfunction and increased intestinal permeability. Regulation of the gut barrier may involve the central nervous system. We hypothesize that vagal nerve stimulation prevents an increase in intestinal permeability after TBI.
  
  
  METHODS
  Balb/c mice underwent a weight drop TBI. Selected mice had electrical stimulation of the cervical vagus nerve before TBI. Intestinal permeability to 4.4 kDa FITC-Dextran was measured 6 hours after injury. Ileum was harvested and intestinal tumor necrosis factor-alpha and glial fibrillary acidic protein (GFAP), a marker of glial activity, were measured.
  
  
  RESULTS
  TBI increased intestinal permeability compared with sham, 6 hours after injury (98.5 microg/mL +/- 12.5 vs. 29.5 microg/mL +/- 5.9 microg/mL; p < 0.01). Vagal stimulation prevented TBI-induced intestinal permeability (55.8 +/- 4.8 microg/mL vs. 98.49 microg/mL +/- 12.5; p < 0.02). TBI animals had an increase in intestinal tumor necrosis factor-alpha 6 hours after injury compared with vagal stimulation + TBI (45.6 +/- 8.6 pg/mL vs. 24.1 +/- 1.4 pg/mL; p < 0.001). TBI increased intestinal GFAP 6.2-fold higher than sham at 2 hours and 11.5-fold higher at 4 hours after injury (p < 0.05). Intestinal GFAP in vagal stimulation + TBI animals was also 6.7-fold higher than sham at 2 hours, however, intestinal GFAP was 18.0-fold higher at 4 hours compared with sham and 1.6-fold higher than TBI alone (p < 0.05).
  
  
  CONCLUSIONS
  In a mouse model of TBI, vagal stimulation prevented TBI-induced intestinal permeability. Furthermore, vagal stimulation increased enteric glial activity and may represent the pathway for central nervous system regulation of intestinal permeability.
authors.affiliation: Department of Surgery, Division of Trauma, Surgical Critical Care and Burns, University of California San Diego, California, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
authors.forename: Todd
authors.initials: T
authors.lastname: Costantini
authors.forename: Seok Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Carrie
authors.initials: C
authors.lastname: Peterson
authors.forename: William
authors.initials: W
authors.lastname: Loomis
authors.forename: James
authors.initials: J
authors.lastname: Putnam
authors.forename: Brian
authors.initials: B
authors.lastname: Elicieri
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications*; D002199:Capillary Permeability; D002490:Central Nervous System / Q000503:physiopathology; D003911:Dextrans; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006706:Homeostasis; D007077:Ileal Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D051381:Rats; D012720:Severity of Illness Index; D016037:Single-Blind Method; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D055536:Vagus Nerve Stimulation / Q000379:methods*; D015431:Weight Loss
chemical_list: D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate
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