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The effect of oxLDL on the release of IL-1 by vascular cells in the brain, possible link with vascular dementia


Project Description

The prevalence of vascular dementia is increasing and atherosclerosis is known to be a major risk factor for this condition. It is known that atherosclerosis in the intercranial arteries in significantly increases the risk of dementia independent of cerebral infarction. We have recently shown in an experimental model that systemic atherosclerosis causes significant neurovascular decline due to a reduction in neural activity, neuronal death and increased inflammation. The most upregulated proteins in the brain in this setting were interleukin-1 and TNF alpha. This project will study the effect of modified lipids e.g. oxLDL on the release of pro-inflammatory cytokines by brain endothelial endothelial cells. The project will also determine the mechanism involved and investigate if release can be blocked by inflammasome inhibitors, IL-1R inhibitors or drugs e.g. statins. The project will also establish a model of the blood brain barrier (BBB) in vitro and test whether oxLDL can lead to increased permeability and loss of function and determine the mechanism of this. In the final part of the project, an in vivo model will be used to assess the effect of oxLDL on BBB function.
This work will shed light on the contribution of oxidised lipids to neurovascular dysfunction in the brain in the setting of atherosclerosis and dementia.

Funding Notes

Funding:
This project is suitable for a self-funded student or a student with a government scholarship including from overseas.

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience. (add any additional requirements here)

The candidates must have completed a laboratory based project as part of their degree.

References

Proposed start date: October 2020

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