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APLP2: A Neuroprotective Receptor For Acute Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$648,739.00
Summary
Traumatic brain injury (TBI) is the major cause of deaths in Australians under 45 years of age. We have shown that the amyloid precursor protein (APP) is protective in models of TBI. To understand how APP is neuroprotective we have isolated APP binding proteins and identified the amyloid precursor-like protein 2 (APLP2) molecule as a strong candidate for the APP-neuroprotective receptor. This grant will investigate the interaction between APP and APLP2 as a novel neuroprotective pathway in TBI.
Serum Neurofilament Light As A Biomarker To Improve Management Of Mild Traumatic Brain Injuries
Funder
National Health and Medical Research Council
Funding Amount
$1,092,781.00
Summary
There is increasing awareness that mild traumatic brain injuries (mTBIs), such as concussions, can lead to persistent or permanent neurological symptoms. Nonetheless, the identification and management of mTBIs remains notoriously difficult. In this proposal, we will assess exactly how a novel blood test can be implemented to assist in mTBI diagnosis, and the identification and management of individuals at risk of suffering persistent or chronic neurological problems.
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
Towards Better Detection And Management Of Sports Concussion In Australia
Funder
National Health and Medical Research Council
Funding Amount
$200,027.00
Summary
The proposed program, in partnership with the AFL, will constitute the cornerstone of a foundation of research into current guidelines for the detection and management of sports concussion. The recent development of non-helmeted accelerometer technology has enabled real-time detection of head impact biomechanics in male and female Australian footballers. Outcomes will inform game day and long term management of sports concussion nationally (elite & amateur), and inform other similar sports
Mild Traumatic Brain Injuries And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$928,690.00
Summary
Repeated mild traumatic brain injuries (RmTBIs) have been linked to the development of neurodegenerative conditions. However, whether RmTBIs cause neurodegenerative disease, and the factors involved, requires further research. Using an innovative rat model, this project will examine whether RmTBIs cause long-term neurological changes resembling neurodegenerative disease. This cutting-edge project is highly relevant to human patients and will improve our understanding of these common injuries.
A Prospective Study Of Concussion In Children And Adolescents: Diagnosis, Recovery And Risk Factors For Poor Outcome.
Funder
National Health and Medical Research Council
Funding Amount
$277,000.00
Summary
Concussion is one of the most common neurological injuries and represents a significant public health issue in Australia. The most common consequences of concussive injuries are reduced attention, slowed response speeds and memory impairment. These cognitive processes are critical for performing common day-to-day activities in childhood and adolescence (e.g. acquiring new knowledge and skills, attending to school work). Approximately 20% of concussive injuries occur during participation in organ ....Concussion is one of the most common neurological injuries and represents a significant public health issue in Australia. The most common consequences of concussive injuries are reduced attention, slowed response speeds and memory impairment. These cognitive processes are critical for performing common day-to-day activities in childhood and adolescence (e.g. acquiring new knowledge and skills, attending to school work). Approximately 20% of concussive injuries occur during participation in organised sport. In adult populations, there are now evidence-based guidelines for the diagnosis and management of concussion in sport. Few well-controlled studies exist to identify the frequency and outcome of such injuries in child and adolescent populations, and there are currently no guidelines for diagnosis and management of concussion in children. Further, the academic and social consequence of concussion for the child remains unknown. This study will investigate the cognitive and behavioural outcomes of concussion in young children and adolescents and will use this information to modify and validate currently available adult concussion diagnosis and management paradigms for application with this population. This study will also investigate risk factors for poor outcome following concussion in children and adolescents, and provide age-appropriate data for use in the medical, behavioural and educational management of concussed children and adolescents. A total of 3000 children aged between 10 and 18 years will be recruited to participate in this study. All participants will undergo a baseline evaluation consisting of memory and attention tests, a behavioural rating scale, and measures of educational ability. Participants parents will also provide general health and demographic information. Children who are concussed during the year will be re-assessed within 48 hours of injury and again at 5 days, 10 days and 30 days post-injury to track recovery.Read moreRead less
Investigating The ‘Silent Epidemic’ Of Mild Traumatic Brain Injury: A TMS-EEG Study
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Mild traumatic brain injury (mTBI) is common following an impact to the head. These injuries can affect brain function for many years after the initial incident, are associated with the development of serious conditions such as depression or Alzheimer’s disease, and increase the risk of suicide. This project will use cutting edge neurophysiological techniques to better understand how mTBI affects the brain, and to identify new strategies for restoring brain function following injury.
Mild Traumatic Brain Injury And The Risk Of Long-term Neurodegenerative And Neurobehavioural Disease
Funder
National Health and Medical Research Council
Funding Amount
$585,269.00
Summary
Considerable media attention surrounds the potential for long-term problems in individuals with high exposure to head impacts such as seen in sporting, civilian and/or military contexts. This study examines the long-term effects of mild traumatic brain injury (mTBI) and helps close the current knowledge gap of the impact of this disorder on individuals. There are no long term trials to answer the critical question of whether mild TBI causes long term problems in the brain.
Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.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