Stimulating the central nervous system to prevent intestinal dysfunction after traumatic brain injury.
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.
Bansal
Vishal
V
Department of Surgery, Division of Trauma, Surgical Critical Care and Burns, University of California San Diego, California, USA.
Costantini
Todd
T
Ryu
Seok Yong
SY
Peterson
Carrie
C
Loomis
William
W
Putnam
James
J
Elicieri
Brian
B
Baird
Andrew
A
Coimbra
Raul
R
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
D003911:Dextrans; D005904:Glial Fibrillary Acidic Protein; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate
J Neurotrauma. 2009 Aug;26(8):1353-9
19344293
Am Surg. 2008 Sep;74(9):866-72
18807680
Shock. 2002 Aug;18(2):169-76
12166782
J Surg Res. 2005 Feb;123(2):188-93
15680377
Crit Care Med. 1999 Nov;27(11):2525-31
10579275
J Trauma. 2002 Feb;52(2):339-45
11834998
Surgery. 2008 Aug;144(2):159-67
18656621
Gastroenterology. 2002 Jul;123(1):163-72
12105845
J Surg Res. 2007 Jan;137(1):53-60
17081567
Shock. 2009 Apr;31(4):416-22
18791495
Curr Opin Crit Care. 2008 Dec;14(6):690-5
19005311
Cell. 1998 Apr 17;93(2):189-201
9568712
J Trauma. 2008 Jan;64(1):131-7; discussion 137-8
18188111
Neurosurgery. 2004 Aug;55(2):416-24; discussion 424-5
15271250
J Exp Med. 2005 Oct 17;202(8):1023-9
16216887
J Trauma. 2002 Dec;53(6):1152-9
12478043
Nature. 2002 Dec 19-26;420(6917):853-9
12490958
Neurocrit Care. 2008;8(2):293-300
17968518
J Trauma. 2007 Jan;62(1):26-33; discussion 33-5
17215730
JAMA. 1994 Jan 19;271(3):226-33
8080494
J Cereb Blood Flow Metab. 2000 Feb;20(2):369-80
10698075
Anat Histol Embryol. 2007 Feb;36(1):62-74
17266671
Nature. 2003 Jan 23;421(6921):384-8
12508119
Neurogastroenterol Motil. 2004 Apr;16 Suppl 1:28-33
15066001
Nature. 2000 May 25;405(6785):458-62
10839541