The impact of acute illness on blood-brain barrier function and risk of 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

Dementia is a syndrome that causes pathological and progressive cognitive deterioration. Most of dementia cases have an unknown origin. Acute illness events often lead to delirium which increases the chances of developing dementia by 8-fold. Brain vascular dysfunction is associated with age-related cognitive decline and inflammatory events. We propose to determine the deleterious effects of an acute peripheral inflammatory insult on a mouse model of vascular dysfunction and to identify the molecular mechanisms that contribute to vascular damage and failed recovery in delirium-associated dementia. This project has two aims:

Aim 1: Determine the effects of an acute peripheral inflammatory insult on vascular function in a pericyte loss model challenged with the bacteria endotoxin lipopolysaccharide (LPS), to model acute illness, by performing magnetic resonance imaging (MRI), immunohistochemistry, and astrocyte endfoot and brain endothelial cell specific proteomics. We will determine if LPS aggravates vascular function and halts recovery in this model, as well as identify potential molecular pathways driving these phenotypes.

Aim 2: Confirm human-disease relevant pathways to focus on therapeutical targets through staining of human brain tissue from healthy controls and patients with dementia that have suffered delirium.

Eligibility

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

Please use this Application Form to apply.