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dc.contributor.authorASWANI, ADen_US
dc.contributor.editorBrohi, Ken_US
dc.contributor.editorThiemermann, Cen_US
dc.date.accessioned2017-01-06T10:43:11Z
dc.date.issued2016-12-14en_US
dc.date.submitted2017-01-05T14:27:51.400Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/18405
dc.description.abstractTrauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ failure (MOF). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MOF are also not fully elucidated. As a result, successful therapies for trauma-related MOF are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through Toll-like receptor (TLR)-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. The first aim of this PhD thesis was to determine whether mtDNA released after trauma haemorrhage is sufficient for the development of MOF. Secondly, I then aimed to determine the extent of mtDNA release with varying degrees of tissue injury and haemorrhagic shock in a clinically relevant rodent model. My final aim was to determine whether neutralising mtDNA at a clinically relevant time point in vivo would reduce the severity of organ injury in this model.en_US
dc.language.isoenen_US
dc.subjectmultiple organ failureen_US
dc.subjectdamage-associated molecular patternsen_US
dc.subjecttrauma haemorrhageen_US
dc.titleTHE IMPORTANCE AND MECHANISM OF MITOCHONDRIAL DAMAGE ASSOCIATED MOLECULAR PATTERNS (DAMPS) IN THE PATHOGENESIS OF TRAUMA HAEMORRHAGE INDUCED INFLAMMATION AND ORGAN INJURYen_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
pubs.notesNo embargoen_US


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    Theses Awarded by Queen Mary University of London

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