Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.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
Central Aortic Blood Pressure In Children: Establishing A Gold Standard Non-invasive Assessment Of Cardiovascular Risk
Funder
National Health and Medical Research Council
Funding Amount
$694,342.00
Summary
The best way of assessing early risk of cardiovascular disease involves measuring blood pressure near the heart (central pressure), but existing devices used in adults for this purpose are inaccurate in children. We will develop a children-specific method and apply it to study early cardiovascular risk in a comprehensive health study of 2000 children Australia-wide. We will also investigate why children with congenital heart disease frequently develop ‘older-adult’ heart disease at a young age.
The Effects Of Tonic Muscle Pain On The Sympathetic And Somatic Motor Systems In Human Subjects
Funder
National Health and Medical Research Council
Funding Amount
$462,948.00
Summary
The main objective of this proposal is to reveal the effects of nociceptive reflexes in humans, and thus identify their functional and clinical implications. By performing invasive recordings from the nerves that control blood vessels and muscles in healthy volunteers subjected to long-lasting (~1 hour) experimental pain, this work will increase our understanding of the adaptive changes that pain induces and improve treatments to prevent pain from becoming chronic.
FUNCTIONAL IMAGING OF THE BRAINSTEM AND CORTICAL SITES OF BLOOD PRESSURE CONTROL IN HUMAN SUBJECTS IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$398,498.00
Summary
Disturbances in cardiovascular control underpin many diseases yet little is known about how the brain controls the heart and blood vessels. This project uses brain imaging (fMRI) and concurrent nerve recording in awake human subjects to increase our understanding of how normal blood pressure is maintained and how different disease states influence this control.
Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occul ....Rhombomeric Topography of Structures in the Adult Mouse: Evidence from Avian Homologies and Transgenic Mice. The brainstem of birds has been shown to be formed by a line of segments, like carriages of a train. The same arrangement exists in the embryos of mammals, but is hidden in the adult mammalian brain. We will transfer our detailed knowledge of bird brains to make a maps of the brainstem segments in adult mice. We will then test this map with special gene markers which will reveal the occult segmental pattern in adult mice. This work will give us a new way of understanding the organisation of brainstem centres that control breathing, cardiovascular functions and emotional states.Read moreRead less
Towards a continuum model of orienting and defensive responses. Orienting (OR) and Defensive Responses (DR) underlie important survival functions of attending to unexpected stimuli and avoiding harm.We will establish the first integrative profile of human OR/DR function, using simultaneous recording of brain activity and 'body' responsivity. Given sex and age variation in OR/DRs, both males and females spanning six decades will be studied. OR/DR abnormalities are associated with major disorders ....Towards a continuum model of orienting and defensive responses. Orienting (OR) and Defensive Responses (DR) underlie important survival functions of attending to unexpected stimuli and avoiding harm.We will establish the first integrative profile of human OR/DR function, using simultaneous recording of brain activity and 'body' responsivity. Given sex and age variation in OR/DRs, both males and females spanning six decades will be studied. OR/DR abnormalities are associated with major disorders of attention and stress, which also vary with sex and age. We will examine relationships between OR/DR function and proneness to these disorders in healthy individuals. The results will provide a framework for developing prevention and intervention strategies.Read moreRead less
Mapping the connectome that controls blood pressure. The connections that an individual brain cell receives from other cells ultimately determines its behaviour. Using a revolutionary new technique, the project will create a map of the brain cells that control blood pressure.
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.