How does infection change behaviour, brain imaging and pathology in a rat model of cognitive impairment and how does this link to human delirium and dementia?

This project is part of a programme of five 4-year PhD studentships addressing the research theme of ‘Acute illness, delirium and long-term cognitive decline in later life: causes and consequences’. Please see [here] for key background information and details of the programme.

Project

In older people, acute infection increases the risk of acute (delirium) and chronic (dementia) brain injury. This is common, and can occur in normal ageing, but is more common in those already with cognitive impairment, with important downstream health and socioeconomic consequences. Cerebral small vessel disease (SVD) is a common cause of cognitive impairment that increases with ageing. We have developed a preclinical animal model of SVD, the transgenic Atp11bKO rat, which has pathological, behavioural and magnetic resonance imaging changes similar to human SVD, increasing in severity with age. We have shown that endothelial dysfunction is a key mechanism in SVD pathology. Endothelial cells interface between blood, where there are changes in infection, and brain, the organ affected by delirium and dementia.

We will use this model to test the hypothesis that acute Strep. pneumoniae lung infection leads to further early and/or later endothelial dysfunction and blood-brain barrier alteration, in this model. We will use behavioural, imaging, pathology and single cell transcriptomic measures, comparing rat with human, to understand the mechanism by which acute infection causes cognitive change in SVD, with the future aim of being able to prevent and/or treat it.

Eligibility

We require a UK 2:1 honours degree, or its international equivalent, in a relevant subject.

Please use this Application Form to apply.