Multimodal Woven BioPolymer Fibre Conduits For Remodelling Damaged Peripheral Nerve
Funder
National Health and Medical Research Council
Funding Amount
$686,901.00
Summary
Damage to peripheral nerve arises as a result of trauma or disease ranging in severity from mild to severe incapacitation. Currently surgeons remove healthy nerve from individuals with nerve damage to repair more important priority nerves. We aim to create an effective implant for nerve repair that totally degrades leaving behind the regenerated nerve. This will eliminate the need for nerve harvesting as well as restoring lost nerve function in individuals with nerve injury.
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.
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
Segmentation Of The Peripheral Nervous System - The Role Of Axon Guidance Factors.
Funder
National Health and Medical Research Council
Funding Amount
$190,331.00
Summary
Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propo ....Injury to the nervous system results in great loss to the individual and society at large. To repair a damaged nerve pathway so that functional recovery may ensue is the pre-eminent goal of neuroscience research. An understanding of how factors that guide nerve processes coordinate the wiring of the nervous system during development of an embryo will provide an insight into what strategy is required to repair a damaged nerve pathway in the mature nervous system. In this research project we propose to investigate what factors guide the formation of the peripheral nervous system which controls the body. We will use a novel model system whereby a whole chick embryo is grown in a culture dish and the developing nerve pathways can be manipulated to discover what are the exact factors that guide nerve processes to wire up pathways to the limbs and other body parts. This research will provide an opportunity to study the basic principles of nerve pathfinding which may then be applied to more complicated circuits within the brain and to the repair of injured nerve pathways.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.
A Novel Sensory Nerve Stimulator To Improve Neuropathy In Patients With Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$407,924.00
Summary
We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter durat ....We have developed a painless, self-applied, cheap, battery powered electrical stimulation treatment that improves sensory nerve function in some people with diabetic peripheral neuropathy. We have tested this technique in laboratory animals and in people with diabetes and have shown it is effective in some. We now propose to test this technique in a large sample of people similar to the participants in the successful group of our pilot study - 55-65 year old people with diabetes of shorter duration. In addition, older people up to 75 years of age, with up to 10 years duration of diabetes will be included separately. If successful, the electrical stimulation could improve sensation leading to fewer ulcerations and amputations. Much suffering and expense would be avoided. - The magnitude of reduction in suffering and expense can be judged from the fact that people with diabetes have 15 times the risk of amputation as do people without diabetes. In Australia half of non-traumatic amputations are done to people with diabetes. Foot ulcers precede amputations in most cases, and in themselves cause much suffering and expense. Australia needs to act on this now because, if current trends continue, the number of people with diabetes will increase as the population ages. -The number of people aged over 65 will increase from around 2.3 million at present to over 6 million in the next half century. The increase in those over 85 will be even more marked with numbers increasing four fold to over one million people. Diabetes affects approximately 23% of people aged 75 or older.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
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
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