Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
An Extended Follow-up Of Stroke Patients For Cognitive Impairment And Neuropsychiatric Disorders: Sydney Stroke Study
Funder
National Health and Medical Research Council
Funding Amount
$321,800.00
Summary
Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not bee ....Vascular Dementia (VaD) is the second most common cause of dementia after Alzheimer's disease. In fact, it may be a preventable cause of dementia. Yet it has been relatively neglected by researchers until the last decade, which has seen an upsurge of interest in this disorder. There is no consensus on the criteria for dementia. The profile of early cognitive impairment due to vascular factors is still poorly understood, and the longitudinal course of VaD as defined by modern criteria has not been studied. There have been few studies of the progressive changes in MRI in patients with cerebrovascular disease. The overlap of VaD and Alzheimer's disease (AD) remains a problem for taxonomists and clinicians. One approach to the study of VaD is to examine a high risk group of subjects longitudinally to determine the early features, the risk factors and progressive changes. With this in mind, we began studying a cohort of stroke patients who are at high risk of VaD, in 1997-1999, and are following them longitudinally. The follow-up is now in its third year, and three neuropsychological assessments and two MRI-MRS scans have been performed. We propose to extend the follow-up to 5 years, with repeat neuropsychiatric, neuropsychological and MRI-MRS investigations, and wherever possible to necropsy, to determine the nature of vascular pathology that underlies cognitive impairment. Our cohort of stroke patients is arguably the most comprehensively assessed such cohorts internationally, and presents an excellent opportunity for a long-term follow-up study.Read moreRead less
Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
Vascular And Neurogenic Determinants Of Hypertension In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,142.00
Summary
You are as old as your arteries, and people with kidney disease have arteries that age fast. They also have overactive sympathetic nerves, and it is not clear if the blood vessels or nerves are responsible for the high blood pressure that puts strain on the heart and other organs of these patients. We will use an animal model to determine if therapy for hypertension reduces the stiffness of blood vessels or elevated nerve activity. Our results will enable better treatments for kidney failure.
THE NATURAL HISTORY OF COGNITIVE IMPAIRMENT AND DEMENTIA IN A STROKE COHORT
Funder
National Health and Medical Research Council
Funding Amount
$290,747.00
Summary
In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large ....In a current NHMRC-funded study, we have examined 200 stroke patients (and 100 control subjects) at 3 months after a stroke and one year later, and identified those who have impairment in memory and other cognitive functions. We have also studied these subjects in detail from a psychiatric perspective and performed brain scans on them using magentic resonance imaging. We find that many stroke patients have problems with their cognitive functioning which has a major impact on their lives. A large number also become depressed. These consequences of stroke are not given sufficient importance by clinicians. The fact that stroke is a common problem in the elderly, and our society is aging, makes this a problem of major public health significance. In the new proposal, we plan to study these subjects up to 3 years with repeat neuropsychiatric assessments and brain scans to investigate the natural history of stroke-related cognitive impairment. We will determine whether further new cases of dementia develop in the period 1-3 years, what happens to the brain lesions picked up on brain scans, and how these deficiencies affect the patients' living status and their longevity. We will be able to determine the factors that lead to a good outcome, and suggest strategies that may be applicable to improve the functioning of these individuals.Read moreRead less
A-Prof Wheatley is a respiratory and sleep disorders physician investigating the pathogenesis, health consequences and management of sleep breathing disorders, including sleep apnoea and snoring.
The Role Of Snoring Vibrations In The Pathogenesis Of Early Carotid Artery Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$593,833.00
Summary
Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. Increasingly it is now recognised that snoring may be an independent risk factor for the development of stroke. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which may damage the artery wall and subsequently lead to stroke. This may lead to new strategies to treat habitual snoring.