Quick Project Snapshot
Central cardiovascular control: uncovering the role of inflammatory cytokines in the area postrema
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 different cytokines such as CX3CL1 (fractalkine) and tumor necrosis factor-alpha (TNF-α) within the area postrema. 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.
For this project we will be asking the following questions:
- What are the cardiovascular effects of CX3CL1 and TNF-α when applied directly to the area postrema?
- Are the cardiovascular effects of these cytokines altered in hypertension and heart failure?
- small animal surgery (induction of myocardial infarction and hypertension)
- stereotaxic microinjections
- tissue sectioning
- microscopy (light, fluorescence, confocal)
Ruchaya et al. (2014) Experimental Physiology, 99(1) 111-122.
Neurovascular Biology Laboratory
Our laboratory is focused on understanding how genetic, neurochemical and structural changes that occur in the brain following myocardial infarction contributes to an overactive sympathetic nervous system and consequently disease progression into heart failure. Current research projects include:
- Identifying and understanding the function of specific cytokines and their role in the brain in increasing sympathetic nerve activity to drive heart failure progression.
- Understanding blood-brain barrier function and how its integrity becomes compromised in cardiovascular diseases such as heart failure.
- Understanding the role of adult neurogenesis and how this might be important for regulating central cardiovascular control in health and disease.
We have recently shown that adult neurogenesis plays a critical role in the regulation of blood pressure. Using a synthetic analogue of the building blocks of DNA our group found that adult neurogenesis in the solitary tract is increased in both genetically and experimentally induced hypertensive models. The main challenge now is to understand how increased neurogenesis within the NTS contributes to hypertension. We believe this research will help us better understand the neurogenic origins of high blood pressure and reveal a new target for treating hypertensive patients.
All Projects by this LabCentral cardiovascular control: uncovering the role of inflammatory cytokines in the area postremaUnravelling the neural circuits that drive increases in sympathetic nerve activity in heart failureNeuroinflammatory mechanisms involved in hypertension and diabetes
In Systems Neurophysiology we seek to learn how the nervous system controls various bodily functions and how that control is altered in disease. Our disease focus includes not only neurological disorders such as epilepsy and multiple sclerosis, but also how the nervous system impacts on non-neurological diseases such as heart failure and inflammatory diseases. A clear understanding of basic mechanisms is crucial in developing better therapies and reducing the impacts of illness.