• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Traumatic Brain Injury (TBI) Causes Alterations in Myeloid Cell Function: Role of Sex Differences and Lung Infection on Overall Outcomes following TBI

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Doran_umaryland_0373D_11070.pdf
    Size:
    4.359Mb
    Format:
    PDF
    Download
    Author
    Doran, Sarah Jean
    Advisor
    Loane, David J.
    Faden, A. I.
    Date
    2019
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Males are nearly 3-times more likely to die from brain injury than females. However, the impact of sex differences in relation to clinical outcomes following TBI is conflicting. Recent studies report that men have an increased risk for lung infection after TBI. Importantly, hospitalized severely injured TBI patients have nosocomial infection rates of 50%. Acute-onset pneumonia represents 30-50% of infections after more severe TBI, leading to increased deaths and disability. The goal of this work was to investigate the role of sex differences and lung infection on overall outcomes following TBI. In a well-characterized murine TBI model, there are increased numbers of infiltrating myeloid cells in male brains as compared to females following injury, correlating with poorer neurological outcomes. However, myeloid cells and microglia in male and female animals showed a similar pattern of activation in response to brain injury- including increased pro-inflammatory cytokines (TNF-α, IL-1β), reactive oxygen species (ROS), and greater phagocytic activity. These these findings suggest that sex differences with regard to immune responses after TBI that may impact overall outcomes. We also examined potential bi-directional brain-lung interactions by examining posttraumatic lung infection at 3- or 60-days after injury. Animals subjected to TBI showed increased mortality after infection with Streptococcus pneumoniae Type 3 (Sp) at both 3 and 60 days post-injury. However, mortality was greater with infection at 60 days following TBI and exacerbated brain injury, with increased markers of neuroinflammation including TNF-α, IL-1β, and NADPH oxidase 2 (NOX2) in the injured cortex. In the lung, TBI followed by infection resulted increased bacterial burden and pathology. Analysis of Ly6C+ infiltrating monocytes in the lungs of mice infected with Sp 3 days post-injury demonstrated that these cells were less able to produce TNF-α, ROS, and IL-1β in response to infection. In contrast, lung-infiltrating Ly6C+ monocytes in mice subjected to infection 60 days post-TBI produced twice as much IL-1β and 50% more ROS as Ly6C+ monocytes from Sham-infected mice. These data show that TBI causes immune alterations, both acutely and chronically, that may contribute to susceptibility to infection.
    Description
    2019
    Molecular Microbiology and Immunology
    University of Maryland, Baltimore
    Ph.D.
    Keyword
    bidirectional effects
    lung infection
    sex differences
    Brain Injuries, Traumatic
    Sex Factors
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/10846
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.