The Role Of SPARC In Regeneration And Neurogenesis In The Central Nervous System.
Funder
National Health and Medical Research Council
Funding Amount
$324,870.00
Summary
Stroke is a leading cause of disability in the elderly. Although the brain has built-in mechanisms for repairing itself, these processes are slow and incomplete. We are investigating how these natural repair mechanisms work and how to stimulate them to improve recovery. Our initial results suggest that a protein called SPARC, which is involved in wound healing outside the nervous system, may be able to recruit new nerve cells and blood vessels to damaged brain tissue.
Blood-Spinal Cord Barrier Structure And Function In Syringomyelia
Funder
National Health and Medical Research Council
Funding Amount
$82,630.00
Summary
Syringomyelia is a disorder in which a fluid-filled cyst forms within the spinal cord. These cysts expand over time resulting in paralysis or even death. Syringomyelia occurs in association with spinal cord injury and a number of congenital conditions. In this project we aim to investigate the underlying cause of cyst formation, which is currently unknown. It is hoped that these studies will improve our understanding of cyst formation and facilitate development of better treatment strategies.
PURINERGIC TRANSMISSION AND CENTRAL AUTONOMIC REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$157,848.00
Summary
The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to mo ....The brain regulates bodily functions in a complex manner. One such example is the regulation of blood pressure and heart rate. This is achieved by an interconnected network of brain nuclei that sense information from the major blood vessels and integrate appropriate responses to maintain the status quo. Chemicals called neurotransmitters convey the nervous messages, and one such example is purines, which include ATP and adenosine. Both ATP and adenosine can act in a number of brain regions to modulate blood pressure and heart rate. This project is designed to characterise the mechanism by which purines act within specific brain nuclei to regulate the cardiovascular system. Considering the large economic burden on the healthcare system caused by cardiovascular disease, this research is vital to increase our understanding of how diseases such as hypertension may be caused, and therefore provide improved therapeutic strategies.Read moreRead less
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
Functional Mapping Of Autonomic Control Circuits In The Human Brain
Funder
National Health and Medical Research Council
Funding Amount
$291,451.00
Summary
Nerves called sympathetic nerves stimulate the heart and raise blood pressure. The brain drives them when we are excited or frightened. It also over-drives them in cardiovascular diseases, and this makes matters worse. This project will use MRI brain scanning to investigate, for the first time, how the cerebral cortex and brain stem act together to control sympathetic nerves. Understanding how this system works normally will help tell us how it may malfunction, and what we can do to correct it.
Forebrain Control Of Cardiovascular Function: Integrative And Cellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$834,233.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what causes this increased sympathetic activity, but one possibility is that it is due to the action of a circulating hormone called angiotensin, which acts on the brain, activating central nerve pathways which ultimately increase sympathetic activity. In this project we aim to test this hypothesis and thus help to unravel the mechanisms involved in the long term control of sympathetic activity and blood pressure.Read moreRead less
Despite advances in medical management, critical care clinicians continue to search for procedures that will improve outcomes in critically ill patients with haemorrhagic shock (a life-threatening fall in blood pressure). Shock is a consequence of an active process triggered by the brain . The proposed research aims to elucidate the precise sequence of brain events that initiate and maintain shock. We will also evaluate the effects of interventions (designed to ameliorate or reverse shock) on th ....Despite advances in medical management, critical care clinicians continue to search for procedures that will improve outcomes in critically ill patients with haemorrhagic shock (a life-threatening fall in blood pressure). Shock is a consequence of an active process triggered by the brain . The proposed research aims to elucidate the precise sequence of brain events that initiate and maintain shock. We will also evaluate the effects of interventions (designed to ameliorate or reverse shock) on the brain events that drive the shock response. The results of this research will offer, for the first time, a rational basis for devising new methods to reverse or ameliorate shock and potentially improve clinical outcomesRead moreRead less
PREMOTOR SYMPATHETIC CONTROL OF BLOOD PRESSURE DURING PSYCHOLOGICAL STRESS: HYPOTHALAMUS VERSUS MEDULLA.
Funder
National Health and Medical Research Council
Funding Amount
$153,616.00
Summary
Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known ....Health and well being depend in large part on a strong and efficient autonomic nervous system. The autonomic nervous system controls blood pressure, heart rate, gastrointestinal function, immune responses and certain forms of pain. Negative emotions can have a strong impact on autonomic function. We have all experienced the sweaty hands, pounding heart and intestinal discomfort when the mail arrives and bad news is expected or when we face a deadline for which we are not prepared. This is known as psychological stress and it is usually associated with anxiety. Unfortunately, it is also the most common form of stress in modern urban life. There are clear indications that when these autonomic changes become chronic they can lead to hypertension, weak immune responses and gastric ulcers. In people already suffering from cardiovascular diseases they can also precipitate cardiac and cerebrovascular accidents. Clearly, the link between psychological stress and the autonomic nervous system needs to be explored in more detail. This project looks at the organization of the neural network in the brain and spinal cord that controls these responses. It uses a simple model of psychological stress in the conscious rat and recent non invasive techniques to record blood pressure and look at neuronal activity. We think that we have identified a group of neurons that may be controlling very specifically this response. It is located in the hypothalamus. The aim of this project is to further test the role of these neurons and find out what is controlling them. They will also be compared to another group of neurons that also controls blood pressure but apparently not in relation to psychological stress. The possibility that the cardiovascular response to psychological stress might be mediated by a specific group of neurons in the brain is a very exciting finding. It could lead to new therapeutic applications for acting against the short and long term effects of stress.Read moreRead less
Inhibition Of Fear Memories By Extinction: Neural Substrates.
Funder
National Health and Medical Research Council
Funding Amount
$234,250.00
Summary
Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relati ....Anxiety disorders [e.g., Post Traumatic Stress Disorder (PTSD)] are the most prevalent type of psychopathology in the industrialised world. They are associated with characteristic behavioural (e.g., heightened startle) and autonomic (e.g., cardiovascular) reactions. These disorders are often characterised as an inability to regulate the emotion of fear. Significant progress has been made in understanding the neural and cellular processes involved in the establishment of fear memories, but relatively little is known about the mechanisms by which fear memories can be inhibited or suppressed. Understanding this latter process is a key to the development of effective treatments for anxiety disorders such as PTSD where the patient suffers from persistent, intrusive, unwanted trauma memories. A common experimental procedure for reducing learned fear is to repeatedly expose the subject to a fear-eliciting stimulus but without any aversive outcome. This procedure leads to a progressive loss, or extinction, of the fear reactions elicited by the stimulus. Historically, the extinction of fear was thought to be due to an erasure of the fear memory. However, recent evidence shows that extinction inhibits, rather than erases, the fear memory. Because the fear memories remain intact, some structure(s) in the brain must inhibit activity in the fear pathway. This project uses extinction of conditioned fear reactions in rat subjects to determine the structure(s) in the brain that inhibit fear memories and their behavioural and cardiovascular expression. It brings together the expertise of four well-established researchers and uses a combination of behavioural, physiological, immunohistochemical, tract tracing, and lesion approaches to achieve this aim. The proposed experiments will reveal the structure(s) in the brain that control the inhibition of fear, as well as the site(s) of this inhibition in the fear pathwayRead moreRead less