Traumatic Brain Injury Causes Increased Gut Permeability by Attenuation of the Tight Junction Proteins Zonula Occludens Protein-l and Occludin
|If you are not a current Kalamazoo College student, faculty, or staff member, email email@example.com to request access to this thesis.
|Sotherland, Paul R., 1953-
|Kroll, Lauren M.
|vi, 23 p.
|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.
|Department of Surgery. University of California. San Diego, California.
|Kalamazoo College Biology Senior Individualized Projects Collection
|Senior Individualized Projects. Biology;
|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.
|Traumatic Brain Injury Causes Increased Gut Permeability by Attenuation of the Tight Junction Proteins Zonula Occludens Protein-l and Occludin