Investigations Of Mechanisms Underlying Autonomic Cardiovascular Regulation In Medial Temporal Lobe Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
People with epilepsy often show disturbed cardiovascular function which may increase mortality risk. This may reflect seizure related disturbances in the autonomic circuitry regulation of the cardiovascular system. We apply advanced brain imaging analysis of altered neural structure, circuit connectivity and function within medial temporal lobe and mid brain, combined with clinical assessment of autonomic function to provide important new insights into cardiac disturbances in epilepsy.
Investigating The Mechanisms That Increase Nerve-evoked Vasoconstriction Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$372,547.00
Summary
People with spinal cord injury not only lose control of their arms and legs but also lose control of their bladder and bowel. They also have poor control of blood pressure and an overfull bladder or bowel can lead to dangerously high blood pressure. In this project, we are investigating how this abnormal high blood pressure is generated. The aim is to develop treatments which target the mechanisms which increase the blood pressure responses elicited by the bladder and bowel.
Neural Versus Humoral Activation Of The Sympathetic Nervous System In Renal Disease
Funder
National Health and Medical Research Council
Funding Amount
$293,567.00
Summary
In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating horm ....In the healthy body, the kidney and the sympathetic nervous system work together to keep our blood pressure in the normal range, both in the short and long term. When people have kidney disease, this system fails and people can develop high blood pressure. High blood pressure can lead to heart attack and stroke, and so is a serious complication for people who already have kidney disease. It has previously been believed that major factors in this process are fluid retention and a circulating hormone called angiotensin II, but we believe that the sympathetic nervous system is also very important. Further, we believe that sensory nerves in the kidney tell the brain something is wrong in the kidney, making the sympathetic nervous system increase blood pressure inappropriately. We will examine the relative role of the sensory nerves and the hormone angiotensin II in driving the sympathetic nervous system to increase blood pressure, using three different rat models of kidney disease. One of these models is a new rat model of polycystic kidney disease, which is the fourth most important cause of renal disease in Australia. We want to determine what parts of the brain are important in the pathway, and will also test treatments that block the two different pathways (nerves vs. hormones) to see what is the most effective way of controlling not only blood pressure but also slowing down the progression of kidney and heart disease. This work is important as it will not only help us understand how the brain and kidney communicate with each other, but will also have the potential to improve quality of treatment for people with kidney diseaseRead moreRead less
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
Unravelling The Neuropathological Basis Of The Gastrointestinal Manifestations Of Parkinson’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$822,957.00
Summary
Parkinson’s Disease occurs in about 1% of the population. It is a distressing, progressive disease that places a severe burden on patients, families and carers. 80-90% of Parkinson’s Disease patients have constipation which causes substantial distress to patients, their families and carers. We have a rational path to therapy for constipation of Parkinson’s Disease that will be pursued in this project
Sympathetic Nervous System Activation In Renal Failure. Its Contribution To Pathogenesis And Progression.
Funder
National Health and Medical Research Council
Funding Amount
$490,796.00
Summary
Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related t ....Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related toxins. However, renal transplant recipients with excellent graft function and no signs of uremia still exhibit increased sympathetic nerve firing. Most interestingly, bilateral nephrectomized patients have nerve firing rates comparable to that of normal control subjects without renal disease. These data suggest that the diseased kidneys exert excitatory effects on the sympathetic nervous system independent of correction of uremia. The proposed study aims to comprehensively investigate the pattern of sympathetic activation both centrally (microneurography) and regionally (radiotracer dilution methodology) in patients with chronic renal failure and end stage renal disease . The effect of the centrally acting sympatholytic drug rilmenidine on sympathetic activity in the setting of renal disease will be assessed. Patients with ESRD waitlisted for kidney transplantation will be studied before and after transplantation. Some of the transplant recipients will also have undergone uni- or bilateral nephrectomy before transplantation which will enable us to further explore the role of the diseased kidneys in sympathetic activation. The results of this study may prove to have significant implications for treatment and prevention of cardiovascular morbid events frequently associated with renal disease.Read moreRead less
Neural Circuits Producing Pelvic Vasodilation In Females
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions ....The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions of these nerves. An important part of this neural pathway is a group of nerve cells in the spinal cord that connects the central nervous system with peripheral nerves in the reproductive organs - these are called preganglionic neurons. Recently we discovered that a major pathway from the spinal cord to the pelvic blood vessels in females leaves the spinal cord at a different level (lumbar) from that thought previously (sacral level). Currently there is no information on how these lumbar preganglionic nerves in females are connected to other nerve pathways that are active during sexual activity, and how they integrate signals from both the internal organs and the brain. We will use an array of modern cellular techniques together with direct observation of dilation in isolated uterine arteries to discover how these nerve cells are wired up in circuits in the spinal cord. This information is vital for us to understand the factors producing increased blood flow in normal sexual activity, and how these might be altered in inflammation or in conditions where there could be selective damage to one nerve pathway and not the other, such as after pelvic surgery, spinal cord damage at different levels, or stimulation of the spinal cord for treatment of chronic pain. Our study also will help understand referred pain and sensations of discomfort in abdominal and pelvic organs.Read moreRead less
Regeneration Of Pelvic Autonomic Axons After Injury
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known abo ....This project is focused on the problem of erectile dysfunction, especially the common situation where this is caused by injury to the penile nerves. These nerves are part of the parasympathetic nervous system . Nerve injury-induced erectile dysfunction is a common problem for prostatectomy patients, with recovery of normal erections occurring slowly, partially or not at all. There is currently no therapy to improve regeneration of these nerves, and this is partly because very little is known about effects of injury on any parasympathetic neurons, and especially for those that are essential for erection. The first aim of this study is to define the key structural and functional changes occurring in penile parasympathetic neurons during regeneration after injury. This fundamental neurobiological knowledge is essential to develop and optimise an future growth treatments. The second aim of the study is to define the effects of a protein, neurturin, on axonal regeneration of penile pro-erectile neurons. Our evidence so far strongly suggests that it is necessary for the early stages of injury responses. Our studies will be performed in mice, where we also have colonies of knockout animals to study the effect of removing neurturin from the regeneration process. Our experiments will include neuroanatomical studies of injured and growing nerves, pharmacology studies on penile smooth muscle (corpus cavernosum) innervation and responsiveness, and tissue culture studies. We will investigate not only the changes that occur following injury to penile nerves, but also the way in which undamaged nerves may assist in returning erectile function.Read moreRead less
Reduced Baroreceptor Reflex Control Of Heart Rate In Chronic Renal Failure
Funder
National Health and Medical Research Council
Funding Amount
$490,288.00
Summary
People with kidney disease are more likely to die of heart disease than their ailing kidneys. One reason is because their hearts do not respond properly to changes in blood pressure, as the nerve circuits controlling the heart become dysfunctional. We will examine where and why components of this circuit are unable to respond to changes in blood pressure. This will help guide new treatments to reduce the incidence of heart disease and risk of death associated with kidney disease.