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Understanding And Preventing Secondary Degeneration Following CNS Injury
Funder
National Health and Medical Research Council
Funding Amount
$409,147.00
Summary
After neurotrauma, tissue escaping initial injury undergoes secondary degeneration; tissue loss spreads, function worsens. In the complex brain and spinal cord it is difficult to distinguish vulnerable tissue. Using the visual system as a model I will precisely identify cells and processes of secondary degeneration, determine if vulnerable tissue can be rescued by drugs stopping toxic calcium influx and if rescued circuits work properly. The work has implications for neurotrauma and glaucoma.
Risk Factors For Serious Farm-work Related Injury Among Adult Males
Funder
National Health and Medical Research Council
Funding Amount
$665,930.00
Summary
This study addresses occupational injury among male adult farm workers. The health and safety performance of agricultural industries is among the worst in Australia. A recently published study of work-related fatalities from 1989 to 1992 found that rural industries ranked third, with a fatality rate 3-4 times that for all industries. The rural industries accounted for 80 deaths annually. Best estimates place the cost of farm injury between $0.5 and $1.29 billion per year. This study is designed ....This study addresses occupational injury among male adult farm workers. The health and safety performance of agricultural industries is among the worst in Australia. A recently published study of work-related fatalities from 1989 to 1992 found that rural industries ranked third, with a fatality rate 3-4 times that for all industries. The rural industries accounted for 80 deaths annually. Best estimates place the cost of farm injury between $0.5 and $1.29 billion per year. This study is designed to contribute to farm injury prevention by: (1) identifying factors associated with a higher risk of serious injury among adult farm workers and (2) determining the proportions of the farm workforce who are exposed to various injury risks. The study will recruit 300 seriously injured or killed farm workers from regional Victoria and collect information about themselves, their working life and the property on which they work. This information will be compared with 600 randomly selected farm workers who are not seriously injured to determine which personal, work and environmental factors place farm workers at higher risk of injury. The study will lead to the development of new or more refined prevention strategies and programs. A study of this kind has not been conducted before in Australia and would contribute to a continuing scientific basis for selection of interventions for farm injury and targeting of prevention programs, at a time of increasing momentum in agricultural health and safety.Read moreRead less
The Neural Reaction To Injury: Clues To The Cause And Prevention Of Acquired Brain Damage And Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$390,326.00
Summary
The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the compl ....The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the complex cellular and gene expression changes that determine the ultimate fate of the cell. Both acquired brain injury and degenerative conditions such as Alzheimer?s disease represent an enormous health, social and economic burden. Furthermore, with predictions that Alzheimer?s disease will increase by 3-4 times by the middle of the next century due to the Oaging? of the population, it is becoming even more crucial to establish effective therapeutic interventions. The animal models investigated in this project can be used to unravel the crucial neuronal alterations associated with head trauma and the early stages of Alzheimer?s disease and, more importantly, may be the key to discovering novel strategies to prevent neuronal degeneration in these conditions.Read moreRead less
Role Of Musculoskeletal Biomechanical Factors In Cartilage Loss In Those Who Undergo Partial Medial Menisectomy.
Funder
National Health and Medical Research Council
Funding Amount
$654,530.00
Summary
The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art me ....The novel outcomes from our project are that we will identify whether musculoskeletal-biomechanical factors that can be modified are associated with adverse cartilage changes in a subgroup of individuals with an increased risk of developing knee OA, those who have undergone an APM. The findings of this research are timely and of major international significance as there is increasing attention being paid to preventing OA rather than merely treating the signs and symptoms. Our state-of-the-art measure of cartilage changes will allow us to detect those at risk much sooner than traditional measures using radiographs. The measures are also leading edge internationally. We chose these specific factors to investigate as there is evidence that they can be modified with appropriate interventions. For example, static joint alignment could be modified with foot orthoses [Crenshaw, 2000 #1016], muscle weakness can be addressed with strength programs and mechanical loading across the knee could be reduced via weight loss programs or techniques to alter gait patterns. Currently, formal supervised post-operative rehabilitation is not routinely prescribed following APM because it is considered a routine procedure. If our research identifies risk factors for increased cartilage loss then we will be able to develop appropriate intervention strategies for individuals following an APM. These interventions can then be formally tested as to their effectiveness in reducing adverse cartilage changes using randomised controlled trials. In particular, this could lead to changes in current post-operative clinical practice for this patient group. Ultimately, this could reduce the risk of OA in the future and the resultant personal and societal costs of this condition.Read moreRead less
Characterisation Of Substance P Antagonists As A Novel Therapeutic Intervention For Use In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of ....Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of a secondary injury process that occurs between hours to days after the insult. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Over the past 15 years, a number of groups, including ours, have been investigating the secondary mechanisms associated with the development of functional deficits after TBI. Our previous studies have demonstrated that decline in brain free magnesium is associated with functional deficits after experimental brain injury, and that magnesium administration after injury can improve outcome. Magnesium is now on clinical trial as a pharmacologic intervention. Recent studies have suggested that magnesium decline facilitates neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Therefore, inhibiting neuropeptide release, or inhibiting substance P binding, may offer a novel therapeutic approach for the attenuation of oedema and development of neurologic deficits after TBI. This proposal will use a combined biochemical, pharmacologic and behavioural approach to characterise the role of neuropeptides in brain trauma, and attempt to develop a novel therapy for use in clinical trauma.Read moreRead less
Neuroprotection By Ndfip1 In Brain Injury - Identifying Targets And Understanding Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$836,225.00
Summary
Brain injury from trauma and motor vehicle accidents is a serious health issue, affecting approximately 30,000 Australians per year. About 10% of the victims suffer serious long term consequences, including mental, physical and behavioural impairment. We have discovered a new brain protein capable of preventing neurons from dying following injury. This grant will improve our understanding of how this protein works, and provide a scientific foundation for devising therapies.