Nanoparticle Based Neurotrophin Delivery To Promote Directed Neurite Growth And Auditory Nerve Rescue Following Deafness
Funder
National Health and Medical Research Council
Funding Amount
$506,724.00
Summary
The cochlear implant provides hearing information to the severe-profoundly deaf by electrically stimulating the auditory nerves of the inner ear. Deafness causes these auditory nerves to gradually degenerate leaving fewer nerves for the cochlear implant to stimulate. We propose to reverse this neural degeneration by delivering therapeutic drugs to the inner ear using tiny nanoparticles. This novel technology is expected to have application in other areas of neural degenerative disease.
Glaucoma is a progressive, poorly understood blinding disease with limited treatment options. It is characterised by the death of the nerve cells in the eye whose fibres form the optic nerve. Results obtained in the current proposal will lead to a better understanding of key features of the early stages of the disease and, additionally, will explore the potential of a novel therapeutic approach based on regeneration of damaged nerve fibres within the optic nerve.
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
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
The Role Of Adipokines In Modulation Of Gastric Vagal Afferent Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$624,535.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals are disordered in obesity and may be influenced by factors released from fat stores in the body. The aim of this project is to determine how these factors interact with gastric nerve satiety signals and thus identify targets for the pharmacological treatment of obesity.
Circadian Control Of Peripheral Gastric Satiety Signals
Funder
National Health and Medical Research Council
Funding Amount
$701,010.00
Summary
When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of o ....When we feel full after a meal it is the result of a variety of different nerve signals from the gut in response to distension of the stomach and specific nutrients. These signals exhibit circadian variations. The aim of this project is to determine circadian control of gastric nerve satiety signals and to determine how this is affected by obesity and what happens when you disrupt circadian rhythm. This will ultimately identify targets and treatment regimes for the pharmacological treatment of obesity.Read moreRead less
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
Although chronic pain is a serious clinical problem, treatments for its alleviation have largely failed, in part because they have not been tailored to the specific origin of the pain. This proposal focuses on rheumatoid arthritis, a common and incurrable source of chronic pain. This study will investigate how specific changes in spinal cord nerve cells contribute to chronic arthritic pain. The outcomes will help identify new targets to treat chronic pain in rheumatoid arthritis.
How Does Inflammation Of The Gut Change Its Sensory Innervation?
Funder
National Health and Medical Research Council
Funding Amount
$613,767.00
Summary
A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for th ....A large number of patients that are referred to gastroenterologists for pain and discomfort from the bowel are offered no effective treatment. This has a large impact on quality of life and often involves invasive tests to rule out inflammatory or cancerous causes. These patients are classified as suffering from irritable bowel syndrome (IBS). Patients who have diagnosable inflammatory bowel disease (IBD) where colonoscopy is positive may suffer similar symptoms but also have no treatment for this type of symptom. It is becoming apparent that a large subgroup of IBS patients have undergone prior infection or inflammation, and that there are in fact changes in the types of cells in biopsies from their gut. Thus there are common features to IBS and inflammation. These may provide a means for us to find new treatments for IBS and IBD symptoms. Mice develop similar microscopic changes in the colon after experimental inflammation to those seen in humans, so we can discover more from this model. We have recently established that there are several types of sensory nerve fibres from the mouse colon and rectum that convey information about contractions, distension and chemical mediators released from tissue to the central nervous system. These are almost certainly responsible for generating symptoms in patients. We aim in this project to discover how these sensory nerves change in their responsiveness to mechanical and chemical stimuli in experimental inflammation. Importantly we shall investigate the mediators that are present in the tissue which may activate sensory nerves and-or the receptors on sensory nerves that may be increased. These experiments we hope will provide a target at which to aim novel drug treatments for symptoms of IBS and IBD.Read moreRead less
Training-induced Restoration Of Topographic Maps And Vision During Opticnerve Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$379,725.00
Summary
The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, h ....The mature brain and spinal cord, or central nervous system (CNS), are extremely complex. A consequence of such complexity is that little if any spontaneous repair or regeneration occurs after damage. Brain injury and para- or quadriplegia thus inflict extremely high costs on the individual and to society, estimated at approximately $1 billion annually in Australia. One of the greatest medical challenges therefore is to restore function following neurotrauma. One of the most exciting advances, however, over the last decade is the recognition that the adult CNS, particularly after damage, does have a capacity for repair and that appropriate neural activity, produced either via relevant experience or specific training, is essential in driving the repair process to produce useful behavioural recovery. One of the clearest examples comes from our laboratory in which we have recently shown that training animals on specific visual tasks during optic nerve regeneration allows useful vision to be restored; untrained animals are blind via the experimental eye. The advantage of the visual system is that it is a relatively simple part of the CNS with one major class of nerve cell projecting to well defined and accessible brain regions. The significance of the project is that, for the first time, we are able pinpoint specific training-induced effects within identified nerve cells and their connections, a task that is much harder within other CNS regions. In particular, we will examine molecular, anatomical and functional changes that are induced via training and explore whether intervention with blockers of inhibitory neurotransmission further improves the beneficial effects of training. Understanding the changes in nerve cells that underlie the positive effects of training after neurotrauma will have implications for the continuing development of rehabilitation strategies for improved recovery after CNS injury.Read moreRead less