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.
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
Central Neural Regulation Of Brown Fat Function – Glucose Sensing And CNS Pathways
Funder
National Health and Medical Research Council
Funding Amount
$761,942.00
Summary
Our research aims to identify how specific brain cells detect changes in glucose levels and how ageing and diet affect their function. We identified a subset of nerve cells that detect changes in glucose and the “hunger” hormone ghrelin, their ability to do so adapting with age and nutritional status. This project will investigate the potential of these nerve cells as targets for therapeutic and diet- intervention strategies to target obesity, diabetes and promote healthy ageing.
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.
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
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
Immediate Cooling And Emergency Decompression (ICED) For The Treatment Of Spinal Cord Injury: Pilot, Safety And Feasibility Studies
Funder
National Health and Medical Research Council
Funding Amount
$600,008.00
Summary
Victims of Spinal Cord Injury are young, have severe paralysis, complex needs and high lifetime costs. Although urgent surgery greatly improves outcome, it is difficult to achieve because of logistical difficulties. To expand the time window for early surgery, it is proposed to immediately cool patients. This project will conduct the pilot studies necessary before commencing a clinical trial of immediate cooling and emergency decompression (ICED) in patients with cervical spinal cord injuries.
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
Ecstasy, Methamphetamine And Their Combination: Assessment Of Adverse Effects
Funder
National Health and Medical Research Council
Funding Amount
$384,250.00
Summary
MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour a ....MDMA (Ecstasy) and Methamphetamine (METH) are popular party drugs that are frequently used by young Australians. Health problems associated with MDMA and METH use are (1) many people suffer complications arising from the high body temperature (hyperthermia) that these drugs produce, and (2) MDMA and METH may both cause long-term loss of key neurotransmitters in the brain. This effect on the brain may well lead to psychological problems such as anxiety, depression, increased impulsive behaviour and memory impairment. However the link between MDMA and METH use and subsequent brain damage is still very controversial. Recently, we have found that when MDMA and METH are combined, a particularly toxic effect is seen with very high body temperatures and lasting adverse effects on mood and brain function. This is a major cause for concern because of evidence that many Australian drug users are combining METH and MDMA on a regular basis. This project will investigate the short and long-term effects of MDMA, METH and METH-MDMA combinations. Phase 1 is aimed at investigating whether different doses of the drugs lead to lasting changes in mood, behaviour and brain function and to compare the relative toxicity of the three treatments. Phase 2 will determine whether lack of fluid intake, high environmental temperatures and advanced age are risk factors in determining the toxicity of MDMA and METH. Phase 3 will assess whether the toxicity of these drug treatments depends upon whether an animal takes the drugs voluntarily or whether they are injected with the drug by the experimenter. The final part of the project will use a wide variety of advanced techniques to track the brain damage caused by these drug treatments given under a range of conditions. The significance of this project will be in increasing our understanding of how MDMA and METH affect the brain and behaviour and how the harms posed by these drugs may be predicted and therefore minimised.Read moreRead less