Cerebral Circulation In Sleep - Physiology & Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$779,650.00
Summary
Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both adults and children. As many as 200,000 Australian adults and 100,000 children are affected. OSA has major medical consequences, amongst the most serious being cardiovascular disease and stroke. This experimental study investigates the blood flow to the brain and heart in normal sleep, and in sleep disrupted by OSA, as many of the ....Prolonged, repetitive episodes of obstructed breathing during sleep (known as obstructive sleep apnoea syndrome or OSA) is a common medical problem that afflicts both adults and children. As many as 200,000 Australian adults and 100,000 children are affected. OSA has major medical consequences, amongst the most serious being cardiovascular disease and stroke. This experimental study investigates the blood flow to the brain and heart in normal sleep, and in sleep disrupted by OSA, as many of the problems associated with OSA may have their origin in disturbance of blood flow to the brain and heart.Read moreRead less
Astrocytic Contributions To Tissue Damage And Dysfunction In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$275,810.00
Summary
Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to o ....Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to open up new avenues for ameliorating damage and improving outcomes for stroke patients. Astrocytes are one of the major populations of cells in the brain. They play key roles in supporting normal brain function and protecting nerve cells in the brain. Because of their many functions, these cells offer considerable potential as a therapeutic target in stroke. Unfortunately, the responses of astrocytes in this disorder are poorly understood due partly to a lack of techniques to distinguish their contributions from that of other cells in the brain. We have recently designed a novel system using antibodies to deliver genes into selected populations of nerve cells in the nervous system and thus to selectively alter the function of these cells. In the proposed study, we will adapt this technique to selectively modify gene expression in astrocytes. We will then apply the procedure to determine the consequences of altering key functions in astrocytes on the brain damage and behavioural changes that develop in an animal model of stroke. The successful completion of this research will provide a powerful means to investigate the function of astrocytes, not only in diseases such as stroke but also in normal brain. We will also gain novel insights into the astrocytic role in the damage and dysfunction resulting from stroke that have potential applications in developing new therapies.Read moreRead less
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Atherothrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$674,880.00
Summary
CRP is a plasma marker that can identify individuals at high risk for heart attack and stroke. Our preliminary data suggests that plasma CRP is not only an innocent marker, but can also be activated and thereby become a strong inflammatory stimulus by changing from a five unit to a single unit form on the surface of activated platelets. We will investigate this CRP activation in vitro, in animal models and in patients, and aim to develop new drug therapies for diseases such as heart attack.
Role Of Advanced Glycated End Products In Mediating Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$414,000.00
Summary
Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attach ....Diabetes is on the increase in the Western world and with this increase comes the burden of increased complications. One of these is atherosclerosis which leads to heart attacks, strokes and gangrene. In this grant we consider the role of a biochemical reaction where sugar attaches to proteins called advanced glycation and how it may promote atherosclerosis. We will use novel drugs to block vessel damage in a model of diabetic mice prone to atherosclerosis. We will also inject these sugar-attached proteins (AGEs) into mice to see how they directly influence the vessel wall. We will characterise molecular and cellular changes in response to these AGEs. These studies will ultimately lead to better treatments to prevent, slow down or reverse blood vessel damage in diabetes.Read moreRead less
Therapeutic Silencing Of Egr-1 By Novel Catalytic Oligodeoxynucleotides For The Treatment Of Acute Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$384,353.00
Summary
Heart attack remains a major health problem. We have identified a gene in the heart which is turned on in the first few hours of a heart attack. We have shown in principle that switching this gene off using a novel synthetic drug, reduces heart attack size. Our project assesses the long term effects of this drug on the heart using state of the art imaging when the the drug is administered in a clinically relevant manner. This study may faciliate a new treatment approach for this condition.
Depressive Illness And The Heart: Identifying The Relation Between Affective Disorders And Coronary Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$503,625.00
Summary
Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial inf ....Major depression is ranked fourth among the 10 leading causes of the global burden of disease and, if epidemiological projections are correct, by 2020 it will reach second place. Patients with depression are at increased risk of developing coronary heart disease. This elevated risk is independent of conventional risk factors such as smoking, obesity, hyperlipidaemia, diabetes and hypertension. Also conclusively demonstrated is the adverse effect of depression in patients following myocardial infarction (MI), which materially increases mortality. The mechanism of increased cardiac risk attributable to depressive illness is at present uncertain but activation of the sympathetic nervous system, exaggerated platelet reactivity and-or altered baroreflex function are likely to be of prime importance. Preliminary data from our laboratory indicates that whole body and cardiac sympathetic nervous activity and cardiac baroreflex sensitivity are modified following antidepressant therapy. Identifying the underlying neurochemical mechanisms responsible for alterations in affective behaviour, and quantifying cardiac and whole body sympathetic activity directly and indirectly, and testing whether therapeutic and behavioural interventions can influence brain neurotransmitter turnover and modify cardiac sympathetic tone, platelet reactivity, and baroreflex function in a fashion likely to reduce cardiac risk, will be an important step forward in alleviating the burden of depressive illness on the community.Read moreRead less
Examining Genome Wide Gene Expression Changes During Cardiac Injury And Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$351,852.00
Summary
Heart attacks are the leading cause of death in Australia. Following a heart attack, the loss of beating heart cells is replaced with a permanent scar and this limits the heart from functioning properly. The zebrafish can uniquely recover from a heart attack. New heart cells are generated rather than scar formation. This project will use the zebrafish to identify new signals that promote heart regeneration and can potentially be applied in human hearts to reverse the damage following injury.