Stroke is a major cause of death and disability worldwide. In stroke survivors one of the most distressing complications is post-stroke cognitive decline, which occurs in up to a third of individuals within five years and impacts significantly on quality of life. Indeed, stroke doubles the risk of later cognitive impairment independently of known vascular dementia risk factors, and with no available treatments, post-stroke cognitive decline is a critically unaddressed and important component of vascular dementia.
Despite strong evidence for the important role of innate and adaptive immunity in stroke, research on inflammation as a cause of post-stroke cognitive decline is limited. Many factors will influence and be influenced by immune status early after stroke, including infection (e.g. pneumonia), a common and severe post-stroke complication. Modifiers of immune status after stroke could therefore be a key determinant of cognitive outcome and represent an attractive therapeutic target.
Working as part of an international Network of Excellence, Stroke IMPaCT (https://stroke-impact.org/) funded by the Leducq foundation this project aims to further understand how immune/inflammatory mechanisms contribute to post-stroke cognitive decline, using mouse models of ischaemic stroke. Work in this project will parallel prospective clinical studies in Manchester and Stanford and benefit from interactions with leading international stroke research laboratories.
Our previous research has identified the pro-inflammatory cytokine interleukin-1 (IL-1) as a key mediator of early brain damage after stroke and here we will extend this work to investigate how IL-1 driven processes might contribute to longer term outcomes after stroke, with a focus on cognitive decline. We will use well established behavioural tests to study behaviour and assess both central and peripheral immune changes using flow cytometry and immunofluorescence. To reveal underlying mechanisms both pharmacological and genetic approaches (gene-deficient mice) will be used.
Ultimately, we expect findings from the project to inform the future design of clinical trials to prevent/slow post-stroke cognitive decline.
Entry Requirements
Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.
https://www.braininflamelab.org/
https://stroke-impact.org/
How to Apply
To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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