Faculty Collaboration Database

Traumatic brain injury and intestinal dysfunction: uncovering the neuro-enteric axis. J Neurotrauma 2009 Aug;26(8):1353-9

Date

04/07/2009

Pubmed ID

19344293

Pubmed Central ID

PMC2989839

DOI

10.1089/neu.2008.0858

Scopus ID

2-s2.0-68349098738 (requires institutional sign-in at Scopus site)   132 Citations

Abstract

Traumatic brain injury (TBI) can lead to several physiologic complications including gastrointestinal dysfunction. Specifically, TBI can induce an increase in intestinal permeability, which may lead to bacterial translocation, sepsis, and eventually multi-system organ failure. However, the exact mechanism of increased intestinal permeability following TBI is unknown. We hypothesized that expression of tight junction protein ZO-1 and occludin, responsible for intestinal architectural and functional integrity, will decrease following TBI and increase intestinal permeability. BALB/c mice underwent a weight drop TBI model following anesthesia. Brain injury was confirmed by a neurologic assessment and gross brain pathology. Six hours following injury, FITC-dextran (25 mg 4.4 kDa FITC-dextran) was injected into the intact lumen of the isolated ileum. Intestinal permeability was measured in plasma 30 min following injection, by using spectrophotometry to determine plasma FITC-dextran concentrations. Whole ileum extracts were used to measure expression of tight junction proteins ZO-1 and occludin by Western blot. TBI caused a significant increase in intestinal permeability (110.0 microg/mL +/-22.2) compared to sham animals (29.4 microg/mL +/- 9.7) 6 h after injury (p = 0.016). Expression of ZO-1 was decreased by 49% relative to sham animals (p < 0.02), whereas expression of occludin was decreased by 73% relative to sham animals (p < 0.001). An increase in intestinal permeability corresponds with decreased expression of tight junction proteins ZO-1 and occludin following TBI. Expression of intestinal tight junction proteins may be an important factor in gastrointestinal dysfunction following brain injury.

Author List

Bansal V, Costantini T, Kroll L, Peterson C, Loomis W, Eliceiri B, Baird A, Wolf P, Coimbra R

Author

Carrie Peterson MD, MS, FACS, FASCRS Associate Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Brain Injuries
Gastrointestinal Diseases
Ileum
Male
Membrane Proteins
Mice
Mice, Inbred BALB C
Occludin
Permeability
Phosphoproteins
Statistics, Nonparametric
Tight Junctions
Zonula Occludens-1 Protein