Innovative And Multi-disciplinary Treatment Strategies For Secondary Degeneration Following Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$455,452.00
Summary
Following injury to the central nervous system the damage spreads into nearby areas, leading to worse outcomes for the patient. The research conducted during this Fellowship will ensure that promising treatment strategies to prevent spreading damage are used in the best way, and will determine the mechanism of action of these treatments.
Optimising Combinations Of Calcium Channel Inhibitors For Treatment Of Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$679,772.00
Summary
Traumatic injury to the central nervous system is made worse by damage that spreads away from the initial point of impact. Excess calcium entering cells is a key contributor to spreading damage but treatment with single calcium channel inhibitors has been disappointing. We will use combinations of calcium channel inhibitors to block multiple calcium channels and ensure the optimised combination is effective in clinically relevant models of neurotrauma.
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.
Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein ....Parkinson's Disease (PD) is one of the most common neurodegenerative disorders. Its incidence increases steadily with age affecting approximately 1% of the population at age 65 and up to 5% by the age of 85. At the time of diagnosis, patients suffer from a range of motor impairments that worsen over time. Pathologically these patients are characterised by the accumulation of a protein known as alpha-synuclein in specific types of nerve cells in their brain. However, the function of this protein is unknown. This proposal will clarify the role of alpha-synuclein in PD and normal CNS function and provide new potential therapeutic targets for the treatment of PD and other neurodegenerative disorders in which oxidative stress, excitotoxicity and central nervous system trauma have been implicated.Read moreRead less
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
Huntington’s disease (HD) is a devastating neurodegenerative disorder which shares several features with Alzheimer’s and Parkinson’s disease (i.e. dementia-like cognitive deficits). There is currently no cure for HD. Using a mouse model of HD and a combination of relevant drugs (i.e. N-Acetylcysteine and deferiprone) targeting two distinct levels of the cascade of events leading to HD, we will slow down the progression of the disease and correct dysfunctions within the brain.
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.
Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, ....Glutathione is a natural antioxidant, which is known to protect cells in the body from chemical damage. A small part of the glutathione in cells is found in the mitochondria, a structure that is involved in producing the chemical energy needed for normal cell function. The mitochondria are also involved under some circumstances in promoting the death of cells. Although glutathione in general has been well studied, much less attention has been paid to the function of glutathione in mitochondria, particularly in cells from the brain. Our recent studies indicate that this mitochondrial pool of glutathione is particularly important in limiting the death of cells from the brain when exposed to damaging substances that are increased in some diseases. Thus, the capacity of mitochondrial glutathione to deal with such substances might be a factor in determining the extent of cell loss in the brain, which is an important determinant of symptoms in some of the major neurological diseases. Consistent with this possibility, we have obtained evidence indicating that decreases in glutathione in the mitochondria contribute to the cell death and brain damage that results from a stroke. In our proposed studies, we will investigate the function of mitochondrial glutathione in the two major cell populations from the brain, neurons and astrocytes. We will characterise the protective role of the glutathione and investigate how it enters the mitochondria and what factors influence the amount that is present. This will provide new insights into the function of glutathione in the mitochondria and could also suggest novel approaches for manipulating this antioxidant pool. We will also study models of stroke and some related brain disorders to more directly test the role of this antioxidant in disease and to assess whether manipulating the content of glutathione in the mitochondria has the potential to reduce damage and improve function in these disordersRead moreRead less
Professor Ashley Bush has extensively researched the contribution of metal biochemistry to Alzheimer�s and Parkinson�s diseases. In the current proposal he will lead the clinical testing of a new drug that combats the abnormal accumulation of metals in Alzheimer�s brain pathology, he will search for abnormal metal-interactions with blood proteins as a potential predictive test, and he will study the roles of various brain proteins in regulating metal levels to maintain healthy function.