Understanding Brain Injury-Induced Immunosuppression and the Relationship to the Development of Infection

Scott, Brittney Noelle Vivian

Understanding Brain Injury-Induced Immunosuppression and the Relationship to the Development of Infection

dc.contributor.advisor	Kubes, Paul
dc.contributor.advisor	Zygun, David A.
dc.contributor.author	Scott, Brittney Noelle Vivian
dc.contributor.committeemember	Kramer, Andreas H.
dc.contributor.committeemember	Ousman, Shalina S.
dc.contributor.committeemember	Schryvers, Anthony B.
dc.contributor.committeemember	Fox-Robichaud, Alison E.
dc.date	2018-11
dc.date.accessioned	2018-06-08T19:18:33Z
dc.date.available	2018-06-08T19:18:33Z
dc.date.issued	2018-06-05
dc.description.abstract	Infection is a leading cause of morbidity and mortality among hospitalized patients. It has become increasingly apparent that patients with neurological injury have an increased risk for infection due to secondary immunodeficiency. Previous work from our research group found a novel role for invariant natural killer (iNKT) cells in stroke-induced immune suppression, characterized by a shift from a Th1- to Th2-dominant systemic cytokine profile and an increased risk for infection. This work better defined the crosstalk that occurs between the brain and systemic immune system after ischemic stroke, however, many questions remained and whether similar mechanisms were involved in other types of brain injury was unclear. Thus, we evaluated the relationship between iNKT cells, Th1 and Th2 systemic cytokine profiles, and the development of infection among critically ill patients with traumatic brain injury and haemorrhagic stroke. We found that these patients had significantly subnormal levels of many immune mediators, including IFN-γ and TNF-α, indicative of systemic immune suppression. Moreover, iNKT cells were activated among these patients and positively associated with plasma Th2/Th1 cytokine ratios. Infection was common and occurred among forty-six percent of the patients. Additionally, we used animal models to investigate traumatic brain injury-induced immune modulation and its relationship to infection. We observed rapid activation of iNKT cells in the circulation and a >2-fold increase in plasma Th2/Th1 cytokine ratios, which peaked at 8 hours after injury. Remarkably, we also observed rapid changes in the lung microenvironment induced by traumatic brain injury, which influenced the outcome after infection. Moreover, in an attempt to better understand the epidemiology of infection among patients with traumatic brain injury, we conducted a systematic review of the world’s literature on this topic. We summarize and discuss the reported occurrence rates of infection, and the microbiology and risk factors associated with different types of infection, among patients hospitalized after traumatic brain injury. This thesis provides new insights into the relationship between brain injury and the development of infection. Understanding the unique risk for infection after acute brain injury will ultimately translate to better prevention and treatment regimens for these patients.	en_US
dc.identifier.citation	Scott, B. N. V. (2018). Understanding Brain Injury-Induced Immunosuppression and the Relationship to the Development of Infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/31974	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/31974
dc.identifier.uri	http://hdl.handle.net/1880/106746
dc.language.iso	eng
dc.publisher.faculty	Cumming School of Medicine
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary	en
dc.publisher.place	Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Traumatic brain injury
dc.subject	Infection
dc.subject	Immunosuppression
dc.subject	Invariant Natural Killer T cells
dc.subject	Cytokines
dc.subject.classification	Microbiology	en_US
dc.subject.classification	Epidemiology	en_US
dc.subject.classification	Immunology	en_US
dc.title	Understanding Brain Injury-Induced Immunosuppression and the Relationship to the Development of Infection
dc.type	doctoral thesis
thesis.degree.discipline	Medical Science
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.item.requestcopy	true