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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
A Randomised, Placebo-controlled Trial Of Erythropoietin In ICU Patients With Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$1,950,735.00
Summary
Patients who suffer a moderate or severe head injury (traumatic brain injury) have a 50% chance of having a long term neurological disability or death. Erythropoietin is a medication which encourages red blood cell formation but its other beneficial effects are likely to improve outcomes after traumatic brain injury. This study will examine the safety and effects of erythropoietin on long term neurological function in patients who have suffered a traumatic brain injury.
Motivational Interviewing With Cognitive-behavioural Therapy For Anxiety And Depression Following Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$458,298.00
Summary
A large number of people with traumatic brain injury (TBI) experience mental health issues such as anxiety and depression. This randomized controlled trial examines the effectiveness of a cognitive behavioural therapy treatment program adapted for individuals with TBI. At the end of the study, recommendations can be made to rehabilitation practitioners and the wider community about management of mental health issues post TBI, to prevent prolonged distress and facilitate recovery.
Shaken Baby Syndrome: Characterization Of A Model And Evaluation Of Novel Pharmacological Therapies
Funder
National Health and Medical Research Council
Funding Amount
$412,460.00
Summary
Shaken baby syndrome is a form of traumatic brain injury in infants less than 2 years of age. It results in death in 10-40 % of cases, and neurological problems in survivors. No treatment exists largely because there is no well characterized model of the syndrome that replicates the human situation. This study will fully characterize our newly developed model of shaken baby syndrome and examine the effectiveness of a novel interventional strategy targeting brain swelling.
A Randomised Controlled Trial Of Prophylactic Hypothermia In Severe Traumatic Brain Injury.
Funder
National Health and Medical Research Council
Funding Amount
$2,061,506.00
Summary
Patients who suffer from a severe head injury (traumatic brain injury) have a 50% chance of having severe long term neurological disability or death. Some of this damage occurs after the initial injury and may be reduced by artificially lowering the body termperature for up to 7 days to protect the brain from further damage. This project will determine if early, sustained cooling is safe and if it can improve the long term neurological outcomes of patients with traumatic brain injury.
To Understand The Role Of The Plasminogen Activating And Matrix Metalloproteinase Systems In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$499,321.00
Summary
Tissue-type plasminogen activator (t-PA) is known for its role as a clot dissolving protein. It is present in the brain and following traumatic brain injury (TBI), it can worse brain cell damage. We have established a mouse model of TBI . We will compare brain damage in mice that are deficient in or have high amounts of t-PA. We will also determine whether the recovery rate post-TBI can be improved using specific t-PA blockers. This project may provide new therapies for TBI.
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