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Nerve growth factors are essential to promote nerve regeneration and are potential drugs for the treatment of nervous disorders such as spinal cord injury. Our recent result demonstrates that the precursor form of the nerve growth factor brain derived neurotrophic factor (proBDNF) is detrimental to an injured nervous system and can cause nerve degeneration. This project further investigates the phenomenon in order to promote treatment of spinal cord injury.
The Neuro-ophthalmological Manifestations Of Human Mitochondrial Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$100,675.00
Summary
Human mitochondrial diseases often result in neuro-ophthalmological abnormalities. We aim to examine a cohort of patients with mitochondrial disease and document the type and degree of neuro-ophthalmological abnormality. We will provide detail on the retina, optic nerve, oculomotor function, eyelids and visual acuity. We will examine the optic nerve in detail and perform optical coherence tomography and visual evoked potentials on each patient. We will compare results to age-matched controls.
Modulation Of Neurotrophin Receptor Signaling: Understanding The Determinants And Phenotypic Consequences.
Funder
National Health and Medical Research Council
Funding Amount
$507,270.00
Summary
Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the p ....Peripheral nerves are complex structures consisting of motor and sensory neurons, their axons, and the cells that support them, Schwann cells. Peripheral neuropathy is a common neurological problem which covers many disorders of the peripheral nervous system. There are predominately two types of neuropathies: those where there is a primary loss or degeneration of neurons and-or their axons; and those where the Schwann cells are lost. These degenerative pathologies have prompted interest in the potential of growth factors as a general therapy for peripheral neuropathy. The neurotrophins are a family of neuronal growth factors that influence many key aspects of neuronal development, as well as the maintenance of the mature peripheral nervous system. Work in cells in vitro and in animal models provides solid support for the hypothesis that the neurotrophins prevent neuronal death. However clinical trials testing the neurotrophins has led to variable results and side effects due to their many effects. To make these therapies useful, it is crucial to expand our knowledge about how they actually work and which of the many responses they induce actually produces their beneficial effect. This project aims to achieve this goal. I have identified a mechanism where neurotrophin signaling is selectively modulated in vitro. The aims of this project are to understand how this modulation of neurotrophin signaling is mediated, to identify the cellular substrates that are selectively activated and to determine what the biological consequences of this modulation are. Only through analyses such as these can we gain new insights into neurotrophin signaling and develop an understanding of how the activities of neurotrophins can be more precisely harnessed to generate new and more productive therapeutic approaches.Read moreRead less
Aberrant Nerve Excitability: An In-depth Study Of HCN Channel Activity In Neurological Disorders (epilepsy And Chronic Neuropathic Pain).
Funder
National Health and Medical Research Council
Funding Amount
$205,315.00
Summary
Chronic neuropathic pain and epilepsy carry a high burden of disease, and have a major impact on health resources. Abnormal nerve excitability is implicated in both conditions. This study evaluates the use of a non-invasive test applied to peripheral nerve in the measurement of nerve excitability in neuropathic pain and epilepsy. The aim is to establish a sensitive biomarker of disease in assessment and diagnosis of patients, and to help direct therapy and measure response to treatment.
Delayed Neuronal Death After Peripheral Nerve And Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes (axons), there is little chance of normal function being restored because few regrowing axons will find appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some damaged nerve cells die over the months that follow an injury. This ....After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes (axons), there is little chance of normal function being restored because few regrowing axons will find appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some damaged nerve cells die over the months that follow an injury. This slow loss of nerve cells can lead to progressive and ongoing deterioration. Given recent advances in our understanding of how to improve axon regeneration, the degree of functional recovery could be disappointing unless we know more about how to prevent these neurones from dying. This project will use rats as experimental animals to try to understand which types of nerve cells are likely to die or survive after injury to peripheral nerve trunks or to the spinal cord. We will investigate two regions of the nervous system that are commonly involved in injuries in people. After injuries to limb nerves, people lose sensation and movement and can unpredictably develop chronic conditions such as neuropathic pain (unrelated to the damage and often occurring spontaneously) as well as poor blood flow and wound healing in the hands-feet. After most injuries to the spinal cord, the lower part of the cord beyond the injury (in particular the lumbosacral cord controlling hindlimb movement and sensation and the function of bladder, bowel and sexual organs) is often disconnected from the brain leading to paralysis and disrupted control of pelvic organ function. We will identify and study specific populations of nerve cells with sensory (mainly pain-sensing) functions and four identified groups of nerve cells in the lumbosacral cord that project to the brain. Once we know which nerve cells do not survive, we will search for the likely causes of their death and ways to prevent it.Read moreRead less
Theoretical And Computational Studies On Voltage-Gated Potassium (Kv) Channels
Funder
National Health and Medical Research Council
Funding Amount
$427,796.00
Summary
The primary aim of the proposed projects is to understand how biological ion channels work. All electrical activities in the nervous system, including communication between cells and influences of hormones and drugs on cell function, are regulated by the opening and closing of ion channels. We will study, applying rigorous physical principles and engineering methods and using powerful supercomputers, a class of biological ion channels, known as the voltage-activated potassium channels.