The Vasoprotective Actions Of Flavonoids In Ischaemia And Hypercholesterolaemia
Funder
National Health and Medical Research Council
Funding Amount
$181,018.00
Summary
Diet has a major influence on the incidence of coronary artery disease. Thus in populations where large amounts of fruits, vegetables and legumes are consumed with a low proportion of food from animal sources there is a relatively lower incidence of coronary artery disease. A possible explanation for the beneficial actions of this diet is that it provides a high level of compounds called flavonoids. Flavonoids have a number of biological actions that may prevent coronary artery disease. Flavonoi ....Diet has a major influence on the incidence of coronary artery disease. Thus in populations where large amounts of fruits, vegetables and legumes are consumed with a low proportion of food from animal sources there is a relatively lower incidence of coronary artery disease. A possible explanation for the beneficial actions of this diet is that it provides a high level of compounds called flavonoids. Flavonoids have a number of biological actions that may prevent coronary artery disease. Flavonoids can relax blood vessels which would improve blood flow to organs. In addition they may lower the level of LDL cholesterol, the bad form of cholesterol that promotes artery narrowing. They may also have actions that prevent damage that normally occurs to organs when there is an interruption to blood flow, such as occurs when someone has a heart attack or stroke. This project will investigate the ability of selected flavonoids to prevent injury to blood vessels that occurs when there is an interruption to blood flow or when cholesterol levels are too high. Understanding the actions of flavonoids may lead to the development of new therapies to prevent or treat heart attacks and stroke.Read moreRead less
Does NADPH Oxidase Link Gender, Hormone Replacement Therapy And Outcome After Stroke?
Funder
National Health and Medical Research Council
Funding Amount
$481,439.00
Summary
This project will assess whether the reduction of a novel mechanism to open brain arteries (i.e. via activation of 'Nox' proteins and generation of oxygen radicals) is a possible explanation of why hormone replacement therapy (HRT) increases the risk of stroke in postmenopausal women. We will compare brain artery function of normal mice with those deficient in certain Nox genes in models of menopause, HRT and stroke. This knowledge should lead to safer stroke therapies in women and men.
Pharmacological Strategies To Prevent Damage To White Matter In The Central Nervous System After Ischaemia
Funder
National Health and Medical Research Council
Funding Amount
$150,770.00
Summary
A stroke is caused by an acute blockade of blood flow to a brain region and in most cases, is caused by a clot in the artery that supplies the oxygenated blood and nutrients such as glucose to that region. Within minutes, the region of the brain that is deprived of blood flow will die and so the functions controlled by that region are lost. In the majority of stroke patients, the middle cerebral artery is blocked and this affects parts of the brain controlling movement of limbs or speech and so ....A stroke is caused by an acute blockade of blood flow to a brain region and in most cases, is caused by a clot in the artery that supplies the oxygenated blood and nutrients such as glucose to that region. Within minutes, the region of the brain that is deprived of blood flow will die and so the functions controlled by that region are lost. In the majority of stroke patients, the middle cerebral artery is blocked and this affects parts of the brain controlling movement of limbs or speech and so these patients suffer permanent disabilities. Not surprisingly, stroke is the most common life-threatening neurological disease and the major cause of disbility in adults over 45 years of age. Apart from the profound effect that stroke has on the patient and family, the annual cost of disability to the Australian community is approximately $ 1 billion. If the disability could be reduced, this could reduce the need for institutionalisation of patients and then the cost saving would be great. So our research is directed towards designing drugs to minimise the disability after stroke. Research in the past has focussed on designing drugs to minimise damage to the grey matter in brain but it is becoming apparent that the white matter in brain is very important for transmitting information and also needs to be protected. We will study the biochemical changes in white matter after a stroke in a rat model and use this information to design in a rational way, novel drugs to minimise damage to white matter (axons), thereby reducing the degree of disability after a stroke.Read moreRead less
The In Vivo And In Vitro Biology Of The Novel Intracellular Ion Channel CLIC1 (NCC27)
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Ion channels are complex proteins that regulate the transports of salts, and essential cell function. We have recently cloned a new ion channel, CLIC1, unique in its location on the nuclear membrane as well as other sites. The function of this channel is uncertain, although we have suggested its association with cell growth and inflammation. We propose to investigate the function of CLIC1, dominantly based on gene knockout animals, in which the CLIC1 gene has been deleted.
Pharmacological Modulation Of Microglial Responses After Transient Forebrain Ischaemia In Rats
Funder
National Health and Medical Research Council
Funding Amount
$170,906.00
Summary
A stroke is caused by an acute blockade of blood flow to a brain region and is normally caused by a clot in the artery that supplies blood to that region. Within minutes, the region of the brain that is receiving no blood flow, dies and so the functions controlled by that region cease. If this region controls key functions such as breathing then the patient dies and this occurs in about one third of patients. However, in the majority of patients, the blockage affects parts of the brain controlli ....A stroke is caused by an acute blockade of blood flow to a brain region and is normally caused by a clot in the artery that supplies blood to that region. Within minutes, the region of the brain that is receiving no blood flow, dies and so the functions controlled by that region cease. If this region controls key functions such as breathing then the patient dies and this occurs in about one third of patients. However, in the majority of patients, the blockage affects parts of the brain controlling movement of limbs or speech and so these patients suffer permanent disabilities. Not surprisingly, stroke is the most common life-threatening neurological disease and the major cause of disability in adults over 45. Apart from the profound effect stroke has on the patient and the family, the annual cost of disability to the Australian community is approx $ 1 billion. If the disability could be minimised by reducing institutionalization then the cost saving would be great. Research is being carried out to define how nerves die when they have insufficient blood supply and progress has been made in understanding the biochemical basis of this process. Such knowledge opens the way for the design of novel drugs to delay nerve death. Our laboratory has been successful in designing a novel drug, AM-36 that minimises nerve death in the forebrain of rats that have had the blood supply to the forebrain interrupted for 3 to 5 hours. A recent report has shown that a stroke in the forebrain can lead to nerve damage in the spinal cord and this could contribute to impaired walking in stroke patients. This is an unexpected finding and this project seeks to define how and when nerves in the spine die after a stroke in the forebrain. Such information should then lead to the rational design of drugs to minimise the death of nerves in the spinal cord as well as in the forebrain.Read moreRead less