Project Aims
We will investigate the role of the enlarged perivascular space (PVS) in cerebral small vessel disease (SVD).
Main Hypothesis: Failing PVS function is a common pathway to brain damage in SVD and other disorders of a vascular or neurodegenerative nature
We have proposed a working model for the pathophysiology of SVD:
- Thickening of the small blood vessel walls leads to reduced blood flow and hypoxia. This hypoxia triggers inflammation.
- Pericyte cells begin to degenerate and trigger opening of the blood brain barrier, adding to the increased inflammation.
- Aggregation of inflammatory cells in the PVS leads to remodelling, and alterations to glymphatic flow including fluid stagnation.
- The additive effects of hypoxia, oedema, inflammation and fluid stagnation leads to myelin loss. This further reduces blood flow, and the vicious cycle continues until patients present with clinical signs.
We will explore each of these steps using a combination of clinical and preclinical research techniques
Ultimately we aim to identify new therapeutic targets for SVD.
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