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Central cardiovascular control: what are the cardiovascular actions of of stromal cell-derived factor 1 (SDF-1) in the area postrema?

Do inflammatory mediators act on the brain to alter how it controls cardiovascular function? Despite a huge global effort working on this question, we don't quite know. This project will investigate the role of an inflammatory mediator in driving changes to the cardiovascular system when applied to a critical brain area important for detecting circulating factors in our blood stream. This project will help us understand how inflammation might effect how our brain controls our heart and blood vessels.

Aims

To elucidate the role of SDF-1 in the area postrema in modulating cardiovascular function

The area postrema is a circumventricular organ located in the brain stem. Because it lacks a blood-brain barrier the area postrema is exposed to a wide range of factors found in the circulation. There is much evidence to suggest that inflammatory cytokines are increased in a number of cardiovascular diseases such as hypertension and heart failure. However, the cardiovascular effect of these cytokines when exogenously applied to the area postrema is not currently known. This project will investigate the effects of the stromal cell-derived factor 1 (SDF-1), within the area postrema. Plasma levels of SDF-1 has been previously shown to be increased in hypertension when administered centrally (via intracerebroventricular cannula) but whether it acts within the area postrema is not known. The successful completion of the project will increase our understanding of the role of cytokines in driving changes in blood pressure at the level of the area postrema and how this signaling might be altered in disease states such as hypertension and heart failure.

A blood vessel in the brain expressing claudin-5, a tight junction protein affected by inflammatory cytokines.

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