Mechanisms And Consequences Of Renal Denervation In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,289,105.00
Summary
Chronic kidney disease (CKD) affects ~10-12% of the adult population and is associated with increased mortality. Activation of sympathetic nerves plays an important role in this scenario. We have pioneered a novel catheter-based approach using radiofrequency-energy to disrupt these nerves and we now aim to assess the mechanisms and consequences of applying this novel technology in patients with chronic kidney disease.
A novel sensory neural circuit has been identified innervating the airways and lungs. The anatomical organisation of this circuit has been described to some extent in previous studies, however there is a significant gap in knowledge with respect to its functional importance. This project will develop methods to address this knowledge gap and in doing so the project will firstly describe how this circuit controls breathing under normal conditions and secondly how this becomes dysregulated during
What Central Mechanisms Increase Cardiac Sympathetic Nerve Activity In Heart Failure?
Funder
National Health and Medical Research Council
Funding Amount
$401,389.00
Summary
Heart failure is a disabling and deadly syndrome that has reached epidemic proportions in western populations. In heart failure, the activity of the sympathetic nerves to the heart is dramatically increased, leading to development of arrhythmias and sudden death. Using our unique model of heart failure, in which we directly record cardiac sympathetic nerve activity, we aim to determine the mechanisms in the brain that cause this large, detrimental increase in nerve activity.
Vasomotor Ganglionic Transmission: The Preganglionic Peptide And The Second Gear
Funder
National Health and Medical Research Council
Funding Amount
$451,896.00
Summary
Blood pressure depends on nerve signals that travel from the central nervous system to blood vessels. In the middle of this pathway is a relay station - the sympathetic ganglion cell. Transmission through this relay station has recently been shown to have not only a fixed but also a variable component - the 'second gear'. The project tests if and how three likely candidate peptide molecules, one in the nerves, two in the bloodstream, control this 'second gear' and hence regulate blood pressure.
Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
Effects Of Ghrelin Receptor Ligands On Cardiovascular Function
Funder
National Health and Medical Research Council
Funding Amount
$516,207.00
Summary
Ghrelin is a hormone that is known to control food intake and growth hormone release. Our recent work shows that compounds that mimic ghrelin�s actions influence blood pressure by their effects in the brain, the spinal cord and on arteries. We will investigate the potential of such compounds to treat blood pressure disorders
Changes In Pelvic Autonomic Neurons After Spinal Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,734.00
Summary
This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic ....This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic autonomic neurons make many new connections between each other, and the types of new connections depend on which spinal nerves have been injured. This leads to the question: are these new connections good or bad? ie are they helpful in trying to get organ control back to normal or will they stop the correct connections from the spinal cord from being made in the future? This project addresses these questions by using sophisticated techniques for staining and visualising individual nerve fibres growing out from the spinal cord. We will track how well these fibres grow back and connect with the pelvic autonomic neurons. In particular, we will see whether they make correct connections, and if these connections are influenced by the new fibres that have grown between the autonomic neurons in the interim period. We will also do physiological tests to see if the new connections have the correct function. The ultimate aim of these studies is not only to understand more about regeneration, but to see what determines whether the correct connections have been made - and ideally, to give us insight into how we can make regeneration work more quickly and accurately. We believe that this work is an important adjunct to other studies on spinal injury, which mostly focuses on regaining voluntary motor control (e.g. walking); however loss of bladder, bowel and reproductive function is another important quality of life issue for spinal injury patients.Read moreRead less