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
Developmental Origins Of Adult Cardiovascular Disease: Vascular Health In The Raine Cohort
Funder
National Health and Medical Research Council
Funding Amount
$1,087,427.00
Summary
The Raine study is a unique long term experiment that has collected extensive pre-birth and childhood data in ~3000 young Australians, who are now 27 years old. We plan to measure the artery health of 1200 of these volunteers and to determine what factors, both before and after birth, influence the presence of early atherosclerosis in humans. This study will guide strategies aimed at early prevention of heart attacks and stroke in humans, by defining the major risk factors.
UTILITY OF NOVEL BIOMARKERS IN THE PREDICTION OF MAJOR COMPLICATIONS OF TYPE II DIABETES MELLITUS
Funder
National Health and Medical Research Council
Funding Amount
$510,639.00
Summary
Diabetes is increasingly common. It can cause a variety of complications, the most serious being heart and kidney disease. The reasons why some patients develop such complications are not fully understood so it is difficult to predict who will be affected. The current project will use samples from a large international study of patients with diabetes to assess whether levels of specific markers in the blood help to predict major complications and clarify why they occur.
Is Sympathetic Activation Beneficial Or Detrimental In Septic Shock?
Funder
National Health and Medical Research Council
Funding Amount
$458,755.00
Summary
Septic shock is a major cause of death in intensive care units. It is associated with large increases in sympathetic nerve activity to the heart and kidneys, which have both beneficial and harmful effects. This project will determine the responses to the increased sympathetic activity in septic shock, the causes of it and whether blocking this activation has an overall beneficial effect. This knowledge is essential before drugs that block sympathetic activation are examined in clinical studies.
Investigation Of The Influence Preterm Birth On Lung Structure And Function In School Age Children.
Funder
National Health and Medical Research Council
Funding Amount
$204,482.00
Summary
Bronchopulmonary dysplasia (BPD) remains the most significant chronic lung complication of premature birth. While some information on the long term respiratory outcomes in BPD exist there are no comprehensive studies linking lung structure, function and respiratory symptoms and relating these changes to neonatal history. Studies of this kind are essential to ensure future healthcare for these children can be planned accordingly.
Functional And Molecular Profiling Of Platelet Hyperactivity In Diabetes - Uncovering Dysregulated And Targetable Pathways For Potential Treatments
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
The major cause of death in diabetes is cardiovascular disease. Diabetic patients are more likely to have hardening of their arteries, and an increased propensity to form pathological blood clots. I propose to characterise platelet “hyperactivity” in diabetes both at a functional and molecular level. This unique approach aims to identify the underlying mechanism of platelet hyperactivity which may be targeted in future treatments.