NEU-HORIZONS: The Neuroprotection And Therapeutic Use Of Riluzole For The Prevention Of Oxaliplatin Neurotoxicity Study.
Funder
National Health and Medical Research Council
Funding Amount
$382,402.00
Summary
Colorectal cancer is the second most commonly diagnosed cancer in Australia, with more than 13500 cases recorded annually. Oxaliplatin is an effective chemotherapy for the treatment of colorectal cancer. The major side-effect of oxaliplatin is the development of nerve damage that leads to loss of feeling in the hands and feet and significant disability. The aim of this study is to conduct a trial of a new treatment for oxaliplatin-induced nerve damage.
Nodal Function In Peripheral Neuroinflammatory Disorders: Target Antigens, Functional Significance And Treatment Response
Funder
National Health and Medical Research Council
Funding Amount
$605,172.00
Summary
Inflammatory neuropathies are autoimmune disorders which produce severe disability and represent a costly burden to the healthcare system, but the causes remain unknown. Recent evidence from our team suggests that antibodies against parts of the peripheral nerve at the node of Ranvier are involved. The project aims to identify these specific targets and monitor treatment responsiveness, stabilise nerve function and prevent persistent disability.
Long-term Nerve Damage In Cancer Survivors: Identification Of Risk Factors And Optimal Assessment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$850,172.00
Summary
Nerve damage following chemotherapy treatment leads to early treatment cessation and long-lasting disability, developing with commonly used chemotherapies. There is a critical need to understand the mechanisms, optimize clinical assessment and develop interventions to prevent nerve damage. This project is designed to detect the impact of long-term nerve damage in cancer survivors and develop a risk profile based on clinical, neurophysiological and genetic factors.
SENSORIMOTOR AND AUTONOMIC DYSREGULATION IN HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES
Funder
National Health and Medical Research Council
Funding Amount
$50,406.00
Summary
Specific genetic mutations can lead to widespread changes in the body. Here we are looking at the congenital Hereditary and Sensory Autonomic Neuropathies, the most common of which primarily affects Eastern European Jews. Affected individuals have difficulty walking and controlling their blood pressure, and also have an indifference to pain. This series of experiments aims to increase our understanding of the underlying neurophysiological disturbances.
Predicting Language Skills From Early Auditory Speech Discrimination In Infants With Hearing Loss: Implications For Early Management And Intervention
Funder
National Health and Medical Research Council
Funding Amount
$706,113.00
Summary
Now that newborn hearing checks are available, hearing loss can be picked up soon after birth and hearing aids are fitted shortly after. Although procedures exist for checking that the devices make sounds audible, there is no way to evaluate their effectiveness for supporting a child’s auditory discrimination. This study aims to 1) develop new clinical tools for assessing infants’ auditory discrimination, and 2) determine whether early discrimination predicts spoken language at 3 years of age.
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
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.
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