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.
Aliskiren: Cardioprotection By Increased Bradykinin Levels?
Funder
National Health and Medical Research Council
Funding Amount
$295,236.00
Summary
Aliskiren is a new treatment for hypertension. Our recent studies indicate that aliskiren may have additional benefits for patients with ischaemic heart disease and heart failure. This research project will investigate the effects of aliskiren in different forms of heart disease in rats, in order to provide information that will help patients obtain the maximum benefit from this treatment.
Nitrous Oxide Anaesthesia And Cardiac Morbidity In Major Surgery
Funder
National Health and Medical Research Council
Funding Amount
$2,952,623.00
Summary
Nitrrous oxide is an anaesthtic gas that has been in use for more than 160 years. It has been considered a safe and cheap drug, but newer anaesthetic drugs and improvements in technology provide alternatives that might be safer. Our recent research has found some potentialy serious (but rare) complications associated with nitrous oxide. These are more likely to occur in people with existing heart disease. The purpose of this study is to investigate the safety of nitrous oxide in such people. Whe ....Nitrrous oxide is an anaesthtic gas that has been in use for more than 160 years. It has been considered a safe and cheap drug, but newer anaesthetic drugs and improvements in technology provide alternatives that might be safer. Our recent research has found some potentialy serious (but rare) complications associated with nitrous oxide. These are more likely to occur in people with existing heart disease. The purpose of this study is to investigate the safety of nitrous oxide in such people. When considering its widespread use in about 90% of all surgery in Australia (and around the world), small differences in outcome would have major implications for healthcare delivery. A large well-designed study is necessary to answer this question. We plan to study 7,000 patients having major surgery from around the world.Read moreRead less
Cardiac Effects Of Exposure To Melbourne Air Pollution Caused By The 2006/2007 Bushfires In Victoria
Funder
National Health and Medical Research Council
Funding Amount
$59,000.00
Summary
This project investigates whether the air pollution that was caused by the 2006-2007 Victorian bushfires, had an effect on the health of people living in Melbourne. Cardiovascular effects will be studied by looking at hospital admissions, out-of-hospital heart attacks and the associated death toll. As it is the expectation that bushfires will increase in the future it is important to determine the impact this may have. This research will inform appropriate public health strategies.
Understanding The Pharmacology Of G-CSF For Treating Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$429,393.00
Summary
Heart attacks remain the most common cause of heart failure. Unlike many other tissues the heart is unable to repair itself. Recently it has been recognised that bone marrow cells promote to a small degree repair. Our research confirms these findings and indicates that these can be affected by substances that increase the circulating bone marrow cell numbers. This project will explore how bone marrow cells improve repair and ways to further improve efficacy.
Heart attacks and stroke, underpinned by atherosclerosis, are the number one cause of deaths in our community. While statin reduces cholesterol, there is no treatment to reduce the inflammation initiated by cholesterol entry into blood vessel walls. Our studies are directed towards precise identification of subsets of an inflammatory cell (B lymphocyte) that promote or attenuate atherosclerosis.Therapeutic targeting of these subsets has potential to reduce the inflammation in atherosclerosis