Quick Project Snapshot
Unravelling the neural circuits that drive increases in sympathetic nerve activity in heart failure
Heart failure (HF) is a major global healthcare problem because of its high prevalence, morbidity, mortality and cost. Patients with heart failure are three times more likely to die within three years than patients diagnosed with cancer. While there has been some improvement in HF treatment over last 30 years, morbidity and mortality remain high. One of the major contributors to disease progression is the rise in sympathetic nerve activity. However, the brain areas responsible for this detrimental increase in sympathetic nerve activity has not been well characterised.
This project will investigate which cardiovascular brain centres are activated in the short and long term after myocardial infarction. This project will be relatively demanding and involve using a number of different techniques including surgery, echocardiography, neuroanatomy and electrophysiology if time permits. The successful completion of the project will increase our understanding of the neural circuitry driving sympathetic nerve increases in heart failure.
For this project we will be asking the following questions:
- Which areas of the brain are activated in the short and long term after a myocardial infarction?
- What are the chemical phenotypes of activated neurons?
- Can this neuronal activation be prevented using the anti-inflammatory compound pentoxifylline?
- small animal surgery (induction of myocardial infarction)
- tissue sectioning
- immunohistochemistry (DAB and fluorescence)
- microscopy (light, fluorescence, confocal)
- in vivo electrophysiology (if time permits)
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.