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
The Role Of SPARC In Regeneration And Neurogenesis In The Central Nervous System.
Funder
National Health and Medical Research Council
Funding Amount
$324,870.00
Summary
Stroke is a leading cause of disability in the elderly. Although the brain has built-in mechanisms for repairing itself, these processes are slow and incomplete. We are investigating how these natural repair mechanisms work and how to stimulate them to improve recovery. Our initial results suggest that a protein called SPARC, which is involved in wound healing outside the nervous system, may be able to recruit new nerve cells and blood vessels to damaged brain tissue.
Raised Intracranial Pressure After Trauma: Characterisation And Development Of Pharmacological Interventions
Funder
National Health and Medical Research Council
Funding Amount
$589,788.00
Summary
Raised intracranial pressure (ICP) commonly occurs after traumatic brain injury (TBI) and is thought to be responsible for up to 50% of all mortality, as well as significantly contributing to the persistent neurological deficits in survivors. Few studies have examined the dynamics of raised ICP after TBI, or its effects on brain oxygenation. This study will fully characterize changes in ICP and brain oxygen after TBI and develop novel treatments to control such changes.
Organic Brain Damage After Non-fatal Opioid Overdose
Funder
National Health and Medical Research Council
Funding Amount
$244,858.00
Summary
The study will provide the first data on the level and nature of brain damage due to opioid overdose. The extent to which overdose survivors suffer brain damage has important implications for clinical management, particularly in relation to behavioural problems. It will also provide the first data on brain damage and drug treatment performance. Screening of those with an overdose history may lead to specialised management of these individuals with the potential for improved treatment outcome.
The overall incidence of primary brain tumours in the Western world is 10 per 100,000 people. Unlike many other tumours, these occur in patients of all ages and comprise the second most common tumour type among children and young adults. Most brain tumours remain incurable. We are using our expertise in the field of neural stem cell research to characterise tumour cells responsible for resistance to treatment, with the final goal of identifying new targets for therapeutic intervention.
Interactions Between Injured Neurons, Astrocytes And Metallothionein
Funder
National Health and Medical Research Council
Funding Amount
$478,067.00
Summary
We have found that the protein, metallothionein, which protects the brain after injury or during neurodegenerative disease acts in a more complex way than previously thought, including a direct action on injured neurons as well as on the originating cell, astrocytes. Elucidating each component of metallothionein action will help us understand how cells interact in the brain after injury, and excitingly, offers an opportunity to develop an enhanced therapeutic strategy based on this protein.
Brain Angiotensin: Generation, Localisation And Physiological Function
Funder
National Health and Medical Research Council
Funding Amount
$209,250.00
Summary
The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the b ....The renin angiotensin system is one of the major homonal systems of the body that regulate the cardiovascular system and bodily salt and water balance. Drugs that inhibit the function of this system by reducing the blood level of the hormone angiotensin II or blocking the receptors at which it acts are in the forefront of treatment of high blood pressure and heart failure. It has been proposed that a separate brain renin angiotensin system exists that is not influenced by angiotensin II in the blood stream because of the blood-brain barrier. Strains of mice in which the genes that code for two components of this system - angiotensin converting enzyme (the enzyme responsible for generating angiotensin II) and angiotensinogen (the protein which gives rise to angiotensin II) provide excellent tools to elucidate this system in the brain. By studying these mice we will be able to determine whether angiotensin converting enzyme is necessary in the brain for foreming angiotensin II, and we will be able to determine the sites in the brain where authentic angiotensin peptides exist. We will also determine whether angiotensin II transmits information between neurons in the brain that play a role in control of the cardiovascular system and body fluid balance.Read moreRead less
Mechanisms Controlling Interneuron Migration And Layering In The Cortex
Funder
National Health and Medical Research Council
Funding Amount
$613,060.00
Summary
This work will increase our understanding of how the brain is assembled and what mechanisms control this process. Understanding this highly orchestrated string of events is vital as abnormal positioning and numbers of neurons are known pathologies in brains of patients with epilepsy and schizophrenia. Using state of the art equipment we can visualize neurons moving in brain slices in real-time and investigate environmental factors involved in this important process.
Roles Of Brain-derived Neurotrophic Factor In The Regulation Of Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$299,625.00
Summary
Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to ....Brain-derived neurotrophic factor (BDNF) is an extraordinary neurotrophin which acts not only as a classical neurotrophic factor to promote neuronal survival and differentiation but also as a neuromodulator to modulate nerve activity. Recently, we found that injection of exogenous BDNF into brain stem triggers a significant increase in blood pressure. The present proposal is to test the hypothesis that BDNF is a physiological neuromodulator regulating blood pressure. The aim of this study is to analyse physiological roles of BDNF in the brains stem and spinal cord in the regulation of nerve activity and blood pressure. The successful execution of the project will significantly enhance our understanding of how blood pressure is controlled by BDNF and nerve activity. The knowledge from this study will form basis for designing new drugs to control high blood pressure.Read moreRead less