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
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.
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
Enhancing Treatment Effectiveness For Psychosocial Disorders After Severe Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$253,750.00
Summary
Motor vehicle accidents are a major cause of severe traumatic brain injury (TBI) leading to lifelong, crippling disability. In NSW alone, there are approximately 770 new cases of severe brain injury each year. These people require extensive inpatient rehabilitation and many go on to rely upon community resources for the rest of their lives. The social and economic cost of such injury is cumulative. TBI is mainly experienced by young adults (18-24 years of age) who have normal life expectancy and ....Motor vehicle accidents are a major cause of severe traumatic brain injury (TBI) leading to lifelong, crippling disability. In NSW alone, there are approximately 770 new cases of severe brain injury each year. These people require extensive inpatient rehabilitation and many go on to rely upon community resources for the rest of their lives. The social and economic cost of such injury is cumulative. TBI is mainly experienced by young adults (18-24 years of age) who have normal life expectancy and each year more casualties are added to this social burden. Adults with TBI frequently experience a reduction in social skills. Loss of social skills presents major obstacles to reintegration into the community by making the sufferer more taxing and less rewarding to interact with socially. This loss of social skills limits their ability to maintain pre-injury relationships, and often creates an off-putting first impression on potential new acquaintances that interferes with their ability to establish new relationships. The following project is designed to develop and evaluate a treatment program to enhance the TBI individual's ability to create a good first impression on meeting new acquaintances - e.g., potential employers, work colleagues, customers, and social acquaintances - and to engage in behaviour that is mutually rewarding. The project will inform current theoretical approaches to remediation, providing an examination of the modifiability of social skills deficits that are the result of underlying cognitive impairments. It will provide a systematic, integrated social skills treatment approach for both individuals and groups where there are currently very few. The identification and refinement of successful treatment techniques will increase the efficiency of brain injury rehabilitation in Australia, improve the quality of life for sufferers of TBI and their families, reduce cost of rehabilitation and reduce reliance upon community resources in the long term.Read moreRead less
Functional Neuroimaging In Mild Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,719.00
Summary
Mild traumatic brain injury (mTBI) represents a significant public health issue in Australian communities. Complications can include prolonged symptoms, depression and progressive deterioration of brain function. Clinical management of mTBI hinges on accurate assessment of recovery. The aim of the current study is to investigate the role of novel functional brain imaging techniques such as diffusion tensor imaging and connectivity studies, in the assessment of brain disturbance following mTBI.
Researching Functioning, Disability And Rehabilitation: Translation Into Policy And Practice
Funder
National Health and Medical Research Council
Funding Amount
$481,167.00
Summary
Appropriate support, including responsive health services, is a key to assisting people with disabilities. Disability is most common in older age but acquired disability, particularly following injury, is important in younger people. This research proposal investigates functioning, disability and rehabilitation across the adult lifespan and aims to translate research findings into policy and practice.
Enhancing Rehabilitation Services For Aboriginal Australians After Brain Injury: Healing Right Way
Funder
National Health and Medical Research Council
Funding Amount
$906,445.00
Summary
This project involves implementation of the first culturally secure intervention package for Aboriginal survivors of brain impairment in Australia. Stroke and traumatic brain injury occur significantly more frequently in Aboriginal populations, yet Aboriginal people are under-represented in rehabilitation programs. The project will improve accessibility to rehabilitation, improve health outcomes, and establish an economic model contributing to sustainability and planning of future services.