Is EphA4 The Major Molecular Regulator Of Axonal Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$491,000.00
Summary
Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contri ....Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contribuing to the enormous personal, financial, and community costs of this problem, estimated to cost the Australian community $200 million a year. In recent years advanced anatomical and molecular approaches to the problem of repair of the central nervous system have provided great insights into the neuronal and glial reactions to neural damage that appear to govern the success or failure of neural regeneration. Our preliminary data indicate that a receptor tyrosine kinase, EphA4, which is important for axonal pathfinding in the developing nervous system, is a potent inhibitor of neural regeneration following spinal cord injury. In this project we will determine the mechanisms by which EphA4 exerts its inhibitory effects, and examine the effect of neutralizing EphA4 signalling on neural regeneration. Success in achieving this result will lead to the development of a therapeutic intervention that we will test in mouse models.Read moreRead less
Investigations Into The Role Of Neurotransmitter Release From Astrocytes In The Hippocampus
Funder
National Health and Medical Research Council
Funding Amount
$233,057.00
Summary
While ten per cent of the brain consists of neurons, responsible for movement and thinking, the rest is made up of cells called glial cells. Scientists have always believed that astrocytes, a type of glial cell known for its distinctive star like shape, provide only mechanical and metabolic support for neurons, by maintaining the environment in the brain. This project will investigate how astrocytes actively regulate neuronal activity and may have important roles to play in learning and memory.
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
A Program Of Research Addressing The Transition From Health To Advanced Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$13,017,057.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treat ....Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treatments that prevent heart attack, heart failure and other serious consequences of atherosclerosis.Read moreRead less
Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
The Effect Of CPAP On Erectile And Endothelial Dysfunction In Impotent Men With Obstructive Sleep Apnea
Funder
National Health and Medical Research Council
Funding Amount
$609,559.00
Summary
Erectile dysfunction is common in men with obstructive sleep apnea, due to vascular damage, which leads to heart attack. CPAP is the preferred treatment for patients with OSA because of its well-proven ability to decrease sleepiness and improve blood pressure control. This study will establish if CPAP can also improve erectile and vascular endothelial dysfunction. These results will shed light on the mechanisms that underpin the relationship between OSA and Erectile Dysfunction.
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.
Efficacy And Mechanisms Of Exercise Training In Diastolic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$385,250.00
Summary
Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrom ....Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrome is most frequently due to ischemic or hypertensive heart disease, and most commonly occurs in the elderly. The optimal management of DHF is not well defined, although some drug trials are currently in progress. A number of studies have shown exercise training to improve functional capacity by 15-20% in typical heart failure. However, training has not so far been trialled in DHF. In this multicenter, multi-disciplinary study, we will study a training and control group to determine whether exercise capacity and DHF symptoms are responsive to exercise training. This work will teach us about the optimum exercise prescription, in terms of the duration and nature of training, as well as the safety and effectiveness of exercise training. By using a number of sensitive measurements of heart and vessel function (in which our group has special expertise), we will identify whether exercise training exerts its effect through improvement in vascular function and myocardial properties. If successful, the clinical implications of this study are that; 1. Exercise training will be adopted to improve functional capacity and symptoms of DHF 2. The merits of aerobic and strength training will be identified in DHF 3. Abnormal blood vessel function will be identified as a major and reversible contributor to DHFRead moreRead less