Written by Joyce Smith, BS. The results of this study demonstrate strong two-way interactions between the brain and gut and underscore the importance of bi-directional gut-brain communication on the long-term effects of traumatic brain injury.
Past research has shown that traumatic brain injury (TBI) can trigger long-term changes in the colon such as mucosal injury, increased gut permeability and mortality 1-3 and that subsequent bacterial infections in the gastrointestinal system can increase delayed post- traumatic brain inflammation and the associated damage to brain tissue for up to 72 hours following a TBI 4. Brain trauma can induce secondary brain injury effects that can continue for years and sustain inflammatory processes, contributing to progressive neurodegeneration and neurological dysfunction 5. People who have survived beyond one year following a TBI are 12 times more likely to die from septicemia (blood poisoning) caused by bacteria and 2.5 times more likely to die of a digestive system problem compared to those who do not sustain such an injury 6. This current study attempts to understand the gut-brain interaction following a TBI and to clarify the bi-directional nature of the process 7. They hypothesize that TBI induces chronic changes which affect responses to an intestinal tract bacterial challenge.7
Researchers induced moderate-level TBI in 6-10 week old C57BL/6 mice by a procedure called controlled cortical impact (CCI group) or by a sham procedure (Control group). Both groups of sham- and CCI- injured mice were euthanized at 24 hours following their brain injury (Phase 1 of study); a second set of mice were challenged with Cr infection at 28 days post-injury, and euthanized 12 days post–infection (Phase 2). Others were euthanized 25 days after the infection cleared.
After subjecting the CCL-injured mice during the chronic phase of TBI with Citrobacter rodentium (Cr), a bacterial species that in mice is equivalent to a human infection of Eschericia coli pathogenic gut bacteria 8, researchers examined the brains and colons of the euthanized mice and assessed the immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation. They found that, compared to the control group, the CCL-injured mice had disrupted tight junction proteins and increased permeability of their colons which could potentially allow for easier bacterial transport to other areas of the body 6. Also of interest was the fact that at both 24 hours and twenty-eight days post-injury there was significantly increased mucosal hyperplasia of the colon and increased muscle thickness as well as significantly increased colon enteric glial cells compared to the sham mice; however, pro-inflammatory cytokine activity (TNFa, IFNy, IL-ß or IL-6) was not increased in the colon. The neurological impairment and chronic neurodegeneration persisted longer than one year: the control mice were not affected.
The enteric Cr infection (post 28 days) in the TBI-induced mice resulted in greater cortical loss. Brain inflammation increased, as evidenced by an increase in brain microglial/macrophage and astrocyte activation, suggesting that the cortical neurodegeneration and subsequent brain inflammation may be directly influenced by gut dysfunction.
These results indicate a strong two-way interaction between the brain and the gut in which a TBI may trigger a vicious cycle of brain injury that causes gut dysfunction and potentially worsens the original brain injury. Hopefully this study will help clarify the incidence of systemic infections following brain trauma and contribute to new treatment interventions. Lead author Dr. Faden states, “These results really underscore the importance of bi-directional gut-brain communication on the long-tern effects of TBI.”
Source: Ma, Elise L., Allen D. Smith, Neemesh Desai, Lumei Cheung, Marie Hanscom, Bogdan A. Stoica, David J. Loane, Terez Shea-Donohue, and Alan I. Faden. “Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.” Brain, behavior, and immunity 66 (2017): 56-69.
© The Authors, Open Access licensed under a Creative Commons Attribution 4.0 International License, http://creativecommons.org/licenses/by/4.0/.
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Posted September 16, 2019.
Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.
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- Ma EL, Smith AD, Desai N, et al. Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice. Brain, behavior, and immunity. 2017;66:56-69.
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