Abstract
The blood-brain barrier (BBB) is the major defensive structure of the CNS regulating passage of substances and cells between the peripheral circulation and the brain. Closely associated with the BBB is the glymphatic system, responsible for brain-wide waste clearance, driven primarily by water flux through astrocyte aquaporin-4. These two systems act together to preserve the delicate environment of the brain and protect it from peripheral challenges.
We have recently identified the BBB as a novel target for the gut-brain axis, the dialogue between microbial communities of the body and the brain, showing circulating microbe-derived mediators to modify BBB function. It is unknown if the glymphatic system is similarly regulated, but glymphatic clearance is known to be impaired in conditions associated with microbial dysbiosis, e.g. liver failure.
This project will combine analysis of in vitro models of the BBB with metabolomics and novel in vivo imaging techniques to investigate how microbial-derived metabolites influence BBB permeability and fluid movement in the brain.
References
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