Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Targeting Tau Phosphorylation To Treat And Prevent Acquired Epilepsy, Neurodegeneration And Neuropsychiatric Disease Following A Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project will explore a new approach to the prevention and treatment of epilepsy and the associated mental health disorders following a brain injury. This involves inhibiting pathological forms of the Tau protein, which has been implicated in the development of epilepsy and neurodegeneration. The drug that will be tested in this study has already been demonstrated to be safe and well tolerated in humans, meaning that a positive result from these studies could be expediently translated into c ....This project will explore a new approach to the prevention and treatment of epilepsy and the associated mental health disorders following a brain injury. This involves inhibiting pathological forms of the Tau protein, which has been implicated in the development of epilepsy and neurodegeneration. The drug that will be tested in this study has already been demonstrated to be safe and well tolerated in humans, meaning that a positive result from these studies could be expediently translated into clinical studies.Read moreRead less
Sensory Cortex Processing Changes Underlying Brain And Behaviour Deficits Caused By Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$576,795.00
Summary
Traumatic brain injury (TBI) from physical head trauma causes behavior and cognitive deficits. The burden for victims, families and the community is enormous: total life-time expenses in moderate-to-severe TBI are estimated to be $8.6 billion in Australia. We aim to elucidate whether changes in how the brain processes sensory information could underlie TBI-induced deficits in complex behaviour and whether these changes will be ameliorated by the three currently-most-promising treatments for TBI.
Functional Neurogenesis In The Injured Neocortex Of The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$966,048.00
Summary
Research over the past couple of decades has revolutionised our understanding of the capacity of the brain to generate new cells, especially following an injury. However, what does remain controversial is whether this phenomenon occurs in all areas of the brain, especially following a severe traumatic brain injury or stroke. This project will examine whether the outer surface of the brain has the potential to generate new cells following a brain injury and whether they become functional.
Substance P Antagonists As A Novel Therapeutic Intervention In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and ....Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and subsequent brain damage in areas surrounding the central region of the stroke. These events develop over hours to days following the stroke and are known as secondary injury. 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. Nonetheless, few interventions are available that can limit this development. Our own recent studies have demonstrated that regions in brains which demonstrate the presence of stroke also exhibit signs of neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death in other tissues. 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. Thus, inhibiting substance P binding may offer a novel therapeutic approach to attenuating oedema formation and the development of neurologic deficits following stroke. This proposal will utilise a combined biochemical, pharmacologic and behavioural approach to characterize the role of neurogenic inflammation in the development of oedema and neurologic deficits following stroke. Moreover, we will develop a novel pharmacotherapy that can potentially be used in the treatment of clinical stroke.Read moreRead less
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
Compromised Fetal Brain Development: Neurogenesis And The Potential For Therapeutic Intervention.
Funder
National Health and Medical Research Council
Funding Amount
$497,280.00
Summary
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and ....Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy) that there is a reduction in neurons and in the connections between them. This may result from a reduction in number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1) determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis, apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.Read moreRead less
Optimum Thiamine Dose For Treatment And Prevention Of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial Targeting Aboriginal People.
Funder
National Health and Medical Research Council
Funding Amount
$1,293,716.00
Summary
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for eff ....Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting.Read moreRead less
Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain and selectively impairs key neuropsychological functions. Alcohol misuse affects processes that control excitability in the brain, leading to the over-stimulation of brain cells. When this continues for long periods the cells are likely to die and most alcoholics misuse alcohol for most of their adult lives. We will study the human brain s capacity to use and respond to glutamate, its major natural ....Brain damage resulting from long-term alcohol abuse is localized to discrete regions of the brain and selectively impairs key neuropsychological functions. Alcohol misuse affects processes that control excitability in the brain, leading to the over-stimulation of brain cells. When this continues for long periods the cells are likely to die and most alcoholics misuse alcohol for most of their adult lives. We will study the human brain s capacity to use and respond to glutamate, its major natural excitant, in the regions that are selectively damaged by alcoholism. How these capacities are affected by heredity, and by diseases commonly associated with alcoholism such as cirrhosis of the liver, will also be explored. If we can understand how selective brain damage occurs in alcoholics we will be better able to devise new drug therapies to combat and prevent it. As well, localized brain damage is a feature of many neurological diseases, so the study will provide a general model of disease mechanisms.Read moreRead less
Prof Alan Connelly is an internationally recognised neuroimaging researcher specialising in MRI. His major areas of research are in the development of new methods to acquire and process MR images of both structural and functional aspects of the brain, and the application of these novel methods to clinical neuroscience problems. His work has had a major impact in the field of epilepsy, where techniques that he pioneered have been widely adopted in specialist epilepsy centres worldwide.