Traumatic Brain Injury Causes Increased Gut Permeability by Attenuation of the Tight Junction Proteins Zonula Occludens Protein-l and Occludin
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Authors
Kroll, Lauren M.
Issue Date
2009
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Millions of individuals sustain traumatic brain injury (TBI) each year in the
United States. In many cases of TBI, the body responds with a cascade of progressive
illnesses, including systemic inflammatory response syndrome (SIRS), multisystem organ
failure (MSOF), and eventual death. SIRS contributes greatly to MSOF by promoting
sepsis through the breakdown and increased permeability of the intestinal epithelium,
normally maintained by the tight junction proteins zonula occludens-l (ZO-l) and
occludin. We hypothesized that TBI would initiate an increase in intestinal permeability
by attenuation of ZO-l and occludin. We used a weight drop model to successfully
initiate moderate TBI in mice. We confirmed the effectiveness and accuracy of the
model by neurological evaluation as well as by histological (brain) procurement and
evaluation. We investigated effects of induced TBI on intestinal epithelium by
histological (intestinal) procurement and evaluation. Intestinal histology .of animals
experiencing TBI demonstrated both blunting and abnormally large spacing of the
intestinal villi, indicating breakdown of the intestinal epithelium following TBI. By both
an in vivo intestinal permeability assay and Western blotting, we found that, in TBI
animals, intestinal permeability increased while intestinal ZO-l and occludin
concentrations decreased when compared to sham animals. In conclusion, we propose
increased intestinal permeability following TBI to be secondary to the attenuation of tight
junction proteins ZO-l and occludin. Ours is one of the first studies to demonstrate this
finding, which has extensive clinical applications for individuals experiencing TBI.
Description
vi, 23 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.