Astrocytic Contributions To Tissue Damage And Dysfunction In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$275,810.00
Summary
Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to o ....Stroke is a primary cause of disability and death in adults. The symptoms of stroke arise from damage to brain tissue following disruptions to blood flow. At present, there are few options for treatments to limit the extent of tissue damage and the consequent disruption to function. Although, there have been considerable advances in understanding the cellular and molecular processes underlying the tissue damage, many issues are unresolved. A better understanding of these processes is likely to open up new avenues for ameliorating damage and improving outcomes for stroke patients. Astrocytes are one of the major populations of cells in the brain. They play key roles in supporting normal brain function and protecting nerve cells in the brain. Because of their many functions, these cells offer considerable potential as a therapeutic target in stroke. Unfortunately, the responses of astrocytes in this disorder are poorly understood due partly to a lack of techniques to distinguish their contributions from that of other cells in the brain. We have recently designed a novel system using antibodies to deliver genes into selected populations of nerve cells in the nervous system and thus to selectively alter the function of these cells. In the proposed study, we will adapt this technique to selectively modify gene expression in astrocytes. We will then apply the procedure to determine the consequences of altering key functions in astrocytes on the brain damage and behavioural changes that develop in an animal model of stroke. The successful completion of this research will provide a powerful means to investigate the function of astrocytes, not only in diseases such as stroke but also in normal brain. We will also gain novel insights into the astrocytic role in the damage and dysfunction resulting from stroke that have potential applications in developing new therapies.Read moreRead less
Signalling Mechanisms Regulating Neurogenesis And Neurite Outgrowth
Funder
National Health and Medical Research Council
Funding Amount
$486,000.00
Summary
Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emer ....Injury and diseases of the central nervous system (CNS), such as traumatic injury, stroke, Parkinson's, Huntington's and Alzheimer's disease, affect a substantial number of Australians each year and often have long-term consequences for sufferers and their families. This is primarily due to a lack of robust repair of the damage and a paucity of therapeutic strategies available for treatment. However, although many hurdles are yet to be faced, there is a substantial body of evidence that has emerged in recent years, that has led to the view that repair of the central nervous system following injury of disease may indeed be a possibility. Effective neural repair is likely to require a multi-factorial approach, including blockage of neuronal death, replacement of lost neurons by neural stem cells, and regulation of appropriate subsequent neurite outgrowth and formation of correct connections. We have shown that a regulator of cytokine signaling, SOCS2, promotes neuronal differentiation and neurite outgrowth. This project aims to continue our investigations of the role of SOCS2 and interacting factors in regulating neuronal differentiation as well as substantially expanding our investigations into the role of SOCS2 in regulating neurite outgrowth, using both in vitro and in vivo models. An understanding of the mechanisms involved in these processes may allow us to derive therapies for the repair of the nervous system after injury or disease.Read moreRead less