A Wireless Electric Nerve-guide For Peripheral Nerve Repair
Funder
National Health and Medical Research Council
Funding Amount
$805,064.00
Summary
We aim to deliver a radical new precision intervention for peripheral nerve repair to improve the lives of people with peripheral nerve damage. Drawing from our recently awarded work on 'electric neural tissue engineering', we will pre-clinically test our invention of a unique clinically-amenable electric nerve-guide (e-nerve-guide), designed to act as a protective nerve conduit and wirelessly electrically-stimulate damaged nerves for their regeneration and restoration of function.
Pathophysiology Of Focal Human Entrapment Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$33,626.00
Summary
Neuropathy patients suffer from tingling, pain, numbness, spontaneous muscle contraction and cramp. The symptoms reflect abnormal activation of the nerve involved. It is known that an external agitation can worsen them, like in carpal tunnel syndrome (CTS). This study aims to investigate if changes in function of axonal membrane ion channel play any part in the symptoms. This will be done by comparing axonal membrane ion channel functions of healthy and CTS patients under external stimuli.
Does The Complement System Contribute To Neuropathic Pain?
Funder
National Health and Medical Research Council
Funding Amount
$262,958.00
Summary
Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes ....Nerve injury often results in increased sensitivity to painful stimuli and the perception of innocuous stimuli as painful; it may also result in spontaneous pain. These disorders of pain sensation due to nerve injury are common, debilitating and difficult to treat. They are symptoms of neuropathic pain. Pain is normally signalled to the brain by sensory nerve cells called nociceptors. Following nerve injury, nociceptors are sensitised by chemicals released by inflammatory cells. This contributes to neuropathic pain. We have evidence that inflammatory responses play a key role in initiating neuropathic pain. Other evidence suggests that the immune system contributes to neurological diseases and accompanying pain (e.g. Guillain-Barr syndrome and multiple sclerosis). We plan to test the idea that a component of the immune system known as the complement pathway contributes to the development of neuropathic pain following peripheral nerve injury. The outcome of this work will be a better understanding of the way in which nerve injury leads to chronic disorders of pain, including increased sensitivity to painful stimuli. This will lead in turn to the development of more effective treatments for neuropathic pain.Read moreRead less
The Role Of Proinflammatory Interleukin-17 (IL-17) And IL-17-producing T Cells In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$470,051.00
Summary
Peripheral nerve injury often results in persistent and debilitating neuropathic pain. My overall objective is to understand the immunological mechanisms responsible for such pain. I plan to test the hypothesis that the proinflammatory cytokine interleukin-17 promotes neuroinflammation and contributes to increased pain sensitivity after nerve injury. This study promises to enhance our understanding of neuroimmune activation in neuropathic pain and offers new opportunities for pain management.
How Amyloid Causes Neurodegeneration: The Role Of Transthyretin In Familial Amyloidotic Polyneuropathy
Funder
National Health and Medical Research Council
Funding Amount
$618,950.00
Summary
This project seeks to understand the biochemical basis of nerve degeneration in a disease known as familial amyloidotic polyneuropathy. This disease is caused by a protein known as transthyretin, which is abnormally deposited around nerves and causes nerve damage. The project is highly likely to provide clues which help us understand some related dementia causing diseases like Alzheimer's disease and prion diseases such as scrapie and mad cow disease.
Understanding The Role Of Regulatory T Cells In Chronic Pain Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$587,046.00
Summary
Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for ....Neuropathic pain is a debilitating condition of chronic pain that develops after damage to the nervous system, and lacks an effective treatment. This project focuses on the novel hypothesis that the immunosupressive regulatory T cells and their mediators play a critical role in controlling neuroinflammation and pain hypersensitivity following peripheral nerve injury. This study promises to enhance our understanding of the neuroimmune activation in neuropathic pain and offers novel approaches for pain management.Read moreRead less
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
Molecular And Cellular Mechanisms Of Axon Guidance In The Vertebrate Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can ....There are, at least, two major obstacles that have to be overcome in the design of therapies to assist the repair of injured brain tissue. First, the nerve cells that are damaged have to be encouraged to regrow - typically this regrowth is inhibited in the brain; and second, this regrowth has to be directed so that the correct connections are re-established. This project will begin to unravel some of the mechanisms that nerve cells use to wire up together during development. This information can be used to assist in trying to modulate and facilitate directed regrowth following injury.Read moreRead less
Deciphering The Mechanisms For Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$496,321.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less
A Molecular Approach To Constructing The Olfactory System
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and ....The olfactory (smell) system is a unique part of the nervous system; nerve cells are generated throughout life and it can regenerate even after injury. It therefore provides an excellent model for examining the growth, development and maintenance of nerve cells. This project will examine the effects on the organisation of the olfactory system when some guidance signals are altered. Information we obtain about how this system develops and regenerates may be useful in treating brain disorders and spinal injuries In the current project we will examine the effects of specific nerve cell guidance molecules by generating transgenic mice that produce these molecules only in the olfactory system. We can then determine what changes occur to the nerve cells when these extra molecules are produced. The results of these experiments will provide important information on the the initial growth and targeting of these nerve cells which may have implications for regeneration of these as well as other nerve cells.Read moreRead less