Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

Abstract

OBJECTIVES:

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury.

METHODS:

Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed.

RESULTS:

Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation.

CONCLUSION:

These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury.

• Authors: Elise L Ma, Allen D Smith, Neemesh Desai, Lumei Cheung, Marie Hanscom, Bogdan A Stoica, David J Loane, Terez Shea-Donohue, Alan I Faden
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 66 Pg. 56-69 (Nov 2017) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 28676351 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Inflammation Mediators

Topics

• Animals
• Brain (pathology, physiopathology)
• Brain Injuries, Traumatic (complications, microbiology, pathology)
• Citrobacter rodentium
• Colon (metabolism, pathology)
• Enteric Nervous System (physiopathology)
• Enterobacteriaceae Infections (complications)
• Gastrointestinal Microbiome
• Inflammation (metabolism)
• Inflammation Mediators (metabolism)
• Male
• Mice, Inbred C57BL
• Neuroglia (physiology)