About the Project
Background: Stroke is the second leading cause of death worldwide and the leading cause of adult neurological disability. Systemic infections have been implicated in the development of ischaemic stroke, clinical studies reporting associations between preceding common infections and stroke occurrence. In addition, preceding infections (such as respiratory tract) worsen outcome in experimental animal models of stroke.
Periodontal disease, associated with oral bacterial infection/biofilm, is the most common inflammatory disease seen in man, affecting almost 50% of the UK population. Periodontal disease has been associated with development of stroke and is also linked to cardiovascular disease. However, it is not yet known if preceding periodontal disease can modulate outcome after stroke.
Hypothesis: This project therefore aims to test the hypothesis that periodontal disease leads to worse outcome in an experimental model of stroke. Objectives/methods: This project will firstly characterise systemic and central inflammatory changes in a mouse model of periodontal disease, with particular focus on changes in the vasculature. Subsequently, effects of periodontal disease on cerebrovascular injury and inflammation in response to experimental stroke will be determined. Finally, we will test if the effect of periodontal disease on stroke outcome is influenced by the presence of relevant co-morbidities (i.e. metabolic syndrome/obesity). The project will also aim to identify mediators between periodontal disease and worse outcome after stroke using transgenic mice and blocking antibodies. Outcome: These studies will determine if stroke is affected by periodontal disease and will highlight the importance of good oral hygiene in maintaining health.
Please direct applications to the principal Supervisor:
[Email Address Removed]
Funding Notes
This 4-year full-time studentship forms one of our PhD opportunities within the MRC Doctoral Training Partnership (MRC DTP) scheme. Funding provides full support for tuition fees, annual tax-free stipend at Research Council UK rates (currently £13, 863) and conference/travel allowance. The project is open to UK/EU nationals only due to the nature of the funding.
Please direct applications in the following format to the principal Supervisor:
CV
Official transcripts
Contact details for two referees
A personal statement (750 words maximum) outlining your suitability for the study, what you hope to achieve from the PhD and your research experience to date.
References
Knight E.M., Martins I.V., Gumusgoz S., Allan S.M., Lawrence C.B. (2014) High-fat diet-induced memory impairment in 3xTgAD mice is independent of changes in amyloid and tau pathology. Neurobiology of aging 35(8):1821-32
Murray KN, Girard S, Holmes EM, Parkes LM, Williams SR, Parry-Jones AR, Allan SM (2014) Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia. Stroke Sep 16. pii: STROKEAHA.114.006613. [Epub ahead of print]
Denes A, Pradillo JM, Drake C, Sharp A, Warn P, Murray KN, Rohit B, Dockrell D, Chamberlain J, Casbolt H, Francis S, Nieswandt, B, Rothwell NJ, Allan SM (2014) Streptococcus pneumoniae infection drives atherogenesis and augments cerebrovascular pathologies in ischaemia via IL-1 and platelets. Ann Neurol 75:670-83.
Lawrence CB, Brough D and Knight EM (2012) Obese mice exhibit an altered behavioural and inflammatory response to lipopolysaccharide. Disease, Models & Mechanisms 5 (5):649-59.
Pradillo JM, Denes A, Greenhalgh AD, Boutin H, Drake C, McColl BW, Barton E, Proctor SD, Russell JC, Rothwell NJ, Allan SM (2012) Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. J. Cereb. Blood Flow Metab. 32:1810-9.
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