A Study Of Mechanisms Of Cognitive Decline In Type 2 Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$510,222.00
Summary
Diabetes mellitus and dementia are major public health problems. Diabetes may increase the risk of dementia. This study aims to uncover the mechanism by which diabetes may increase dementia risk. This may lead to finding new ways to prevent or treat diabetes-related dementia and thus reduce the public health burden of dementia.
Nox4-containing NADPH-oxidase As A Protective Enzyme In The Cerebral Circulation
Funder
National Health and Medical Research Council
Funding Amount
$515,812.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activa ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activation of an enzyme, Nox4-containing NADPH-oxidase, to generate oxygen radicals which then relax the wall of blood vessels causing the arteries to let more blood through. We believe that this process plays an important role in the normal, healthy maintenance of blood supply to the brain. Furthermore, we propose that the activity of this enzyme is elevated and therefore protective in brain arteries during high blood presure - which is the major risk factor for stroke. We will specifically test whether the activity of this enzyme actually helps to limit the amount of brain death following stroke. We will use a variety of techniques to assess the importance of this enzyme in brain arteries in the living body, and also in isolated segments of brain artery from animals that are either healthy or have diseased brain arteries. The results are expected to provide major new insight into processes that help maintain brain blood flow under normal conditions and after a stroke, and the knowledge gained here should lead to safer therapies to prevent or treat stroke.Read moreRead less
MECHANISMS OF CEREBROVASCULAR REGULATION IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$216,430.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the degree of opening of the cerebral arteries. This mechanism involves activation of an enzyme, Rho-kinase, which is present in the wall of blood vessels. The applicants believe that this process plays an important role in the normal, healthy regulation of blood supply to the brain. Moreover, there are strong reasons for us to speculate that the function of this enzyme is abnormally high in two disease states that are associated with an increased risk of stroke - high blood pressure and subarachnoid haemorrhage. We will employ a variety of techniques to assess the importance of Rho-kinase in cerebral artery function in the living body, and also in isolated segments of artery. The results are expected to provide major new insight into mechanisms that regulate brain blood flow, and the knowledge gained here may lead to better therapies to prevent or treat stroke.Read moreRead less
Type 2 Diabetes Mellitus And Cognitive Decline - A Longitudinal Study Of Effects And Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$1,317,589.00
Summary
Diabetes mellitus and dementia are major public health problems. Diabetes may increase the risk of dementia. This longitudinal study aims to uncover the mechanism by which diabetes may increase dementia risk. This may lead to finding new ways to prevent or treat diabetes-related dementia and thus reduce the public health burden of dementia.
HMGB1, A Cytokine Linking Inflammation, Lipid Accumulation, And Platelet Activation In Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$519,715.00
Summary
Atherosclerosis, or hardening of large arteries is the underlying cause of up to 50% of deaths in Western communities, primarily from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the accumulation of fats such as cholesterol into the inner lining of blood vessels including those supplying vital organs such as the heart and brain. This study focuses on understanding how a major inflammatory factor, HMGB1, influences this disease process.
Atherosclerosis: Molecular Mechanisms Of Suppression By CD4+CD25+ Regulatory T-cells
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Atherosclerosis, or hardening of large arteries is the underlying cause of up to 50% of deaths in Western communities, primarily from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the accumulation of fats such as cholesterol into the inner lining of blood vessels including those supply vital organs such as the heart and brain. This study focuses on understanding how to use the body's own anti-inflammatory cells suppress inflammation.
Atherosclerosis: Molecular Action And Suppression Of NKT Cell Subsets
Funder
National Health and Medical Research Council
Funding Amount
$458,815.00
Summary
Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed ....Atherosclerosis, or hardening of large arteries, is the underlying cause of up to 50% of deaths in Western communities from heart attacks and strokes. Today it is considered a chronic inflammatory disease arising from the influx of fats such as cholesterol into the inner liming of arteries that provide blood supply to organs such as the heart and the brain. However, the exact role that inflammation plays in the development of this blood vessel disease is poorly understood. This study is directed towards understanding the role of a subset of while blood cells known as NKT cells in the inflammatory process. In particular we will examine whether the activity of NKT cells in promoting atherosclerosis can be controlled either by the administration of drugs that deprive them of molecules that stimulate their activity and-or by the injection of another population of white blood cells known as regulatory T cells that may to limit their activity. Our preclinical study of atherosclerosis in mice has potential for extension to the control of atherosclerosis in humans. Successful translation in this way can be expected to provide a significant health benefit.Read moreRead less
Mechanisms Responsible For Hypertension Caused By Perinatal Omega-3 Fatty Acid Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$280,650.00
Summary
Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) ....Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) for the first time that the essential omega-3 fatty acid, alpha-linolenic acid (ALA), supplied in the early developmental period, affects blood pressure later in life. The work showed that moderate omega-3 fatty acid deficiency in the perinatal period resulted in hypertension, despite reversal of the deficiency at a time months before the assessment of blood pressure. These findings are suggestive of a critical period, during which time the development of normal blood pressure control mechanisms appears, at least partially, dependent upon the supply of omega-3 fatty acids. These findings suggest that omega-3 deficiency early in life may affect fatty acid metabolism, transport or uptake systems, such that re-feeding of the nutrients is functionally ineffective. Alternatively, deficiency of omega-3 fatty acids early in life may arrest development of one or more of the key signalling pathways in the control of blood pressure, such as the Brain Angiotensin System. The influence of dietary omega-3 fatty acid supply, relative to the critical period, on expression of genes involved in the control of blood pressure as well as in fatty acid metabolism, will be defined. Also, the role of the brain angiotensin system in omega-3 fatty acid deficiency-induced hypertension will be determined. We expect that the results of this study will profoundly affect hypertension research, as well as nutrition, particularly that for infants.Read moreRead less
A Population-based Study Of Cerebrovascular Mechanisms Underyling Gait, Balance And Cognition In Older People
Funder
National Health and Medical Research Council
Funding Amount
$528,330.00
Summary
Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the ....Mobility problems, falls and dementia are among the major problems affecting older Australians with significant consequent disability. Treatment of such disorders carries an estimated annual cost of around 4 billion dollars. This study will examine the role of age-related brain changes in causing problems with walking, balance and cognitive abilities in the general community. The clarification of the role of the ageing brain in causing such disorders will guide efforts directed at preventing the occurrence of falls and dementia.Read moreRead less
ROLE OF A DOWN SYNDROME-RELATED PROTEIN IN STROKE OUTCOME
Funder
National Health and Medical Research Council
Funding Amount
$931,302.00
Summary
This project will test whether a gene called DSCR1, which is present at a higher level in Down Syndrome individuals, might play a protective role in the outcome after stroke. We will identify the cells and molecular pathways that are involved in this protective effect in mice, with a longer term view of applying this information to the development of new types of targeted therapies for clinical stroke.