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    Impact of Colonic Inflammation During Chronic Experimental Traumatic Brain Injury in Mice on Long-Term Outcomes

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    Hanscom_umaryland_0373D_11204.pdf
    Embargo:
    2021-07-01
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    Author
    Hanscom, Marie cc
    0000-0001-8308-135X
    Advisor
    Shea-Donohue, Terez
    Faden, A. I.
    Date
    2020
    Type
    dissertation
    
    Metadata
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    Abstract
    Disruptions in the bidirectional communications of the brain-gut axis are increasingly implicated in the onset and progression of a variety of gastrointestinal and neurological disorders, diseases, and injuries including traumatic brain injury (TBI). In addition to the effects in the brain, TBI can result in gastrointestinal dysfunction, potentially affecting TBI pathogenesis and outcomes. This preclinical study examined the effects of colonic inflammation induced during chronic (long-term) experimental TBI on TBI-associated neurobehavioral and neuropathological outcomes. Additionally, the potential involvement of the neural and immunological pathways of the brain-gut axis in colonic inflammation induced changes in neurobehavior and neuropathology was examined. Dextran sodium sulfate (DSS) was administered to adult male C576Bl/6 mice 28 days following craniotomy (Sham) or TBI for 7 days to induce colonic inflammation (DSS injury phase), followed by a return to normal drinking water for an additional 7 to 28 days for recovery (DSS recovery phase). Uninjured animals (Naïve) served as an additional control group. Colonic inflammation during chronic experimental TBI in mice persistently exacerbated deficits in fine motor coordination and anxiety-like behavior and induced deficits in social behavior in TBI-injured mice. These behavioral changes were associated with an induction, or exacerbation, of ipsilateral hippocampal neuronal cell loss and microglial activation in Sham and TBI mice subjected to acute DSS administration, respectively. Colonic inflammation resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes (mLN) in all DSS experimental groups. A sustained increase in spleen and mLN weights in all DSS groups, and thymus weight in Sham and TBI mice administered DSS, was observed up to 28 days following DSS administration. Dysautonomia was also induced in Sham and TBI mice subjected to acute colonic inflammation, with increased sympathetic tone beginning during DSS injury phase and persisting through the end of the first DSS recovery week. These data show that acute colonic inflammation during chronic experimental TBI results in enhanced neurocognitive deficits, neurodegeneration, microglial-related neuroinflammation, and a sustained systemic immune response with altered autonomic balance.
    Description
    Molecular Medicine
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    acute colitis
    colonic inflammation
    neurodegeneration
    neuroinflammation
    traumatic brain injury
    Behavior
    Brain Injuries, Traumatic
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14502
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    Theses and Dissertations School of Medicine
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