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
The Role Of Psychosocial Factors On Recovery Following Early Brain Insult.
Funder
National Health and Medical Research Council
Funding Amount
$255,475.00
Summary
Early brain insult (EBI) is a major cause of developmental delay and long-term disability. However, outcome following EBI is variable and dependent on multiple injury-related and non-injury-related factors. To date, most research has focussed on injury-related variables such as age at insult, nature of brain pathology, and size and site of brain lesion. These injury-related factors predict short-term recovery following EBI, however they have been found to account for a surprisingly modest portio ....Early brain insult (EBI) is a major cause of developmental delay and long-term disability. However, outcome following EBI is variable and dependent on multiple injury-related and non-injury-related factors. To date, most research has focussed on injury-related variables such as age at insult, nature of brain pathology, and size and site of brain lesion. These injury-related factors predict short-term recovery following EBI, however they have been found to account for a surprisingly modest portion of variance in long-term outcome. Thus, non-injury-related factors must also contribute to outcome following EBI. Research now suggests that psychosocial characteristics (social status, environmental conditions, parenting characteristics, family dynamics) influence long-term outcome following EBI, however these studies have focussed on bivariate relationships, relied on specific patient groups limiting the generalisability of findings, and utilised small to moderate samples that are inadequate when investigating complex interactive relationships. As a consequence, the role of psychosocial factors on recovery following EBI is still unclear. The objective of this project is to undertake a large-scale investigation of the independent and interactive contribution of social status, environmental conditions, parenting characteristics and family dynamics on outcome following EBI. The aim is to identify the psychosocial characteristics that predict outcome, mediate recovery, and buffer the impact of injury-related factors in children with EBI. Understanding these complex inter-relationships is crucial for rehabilitation purposes, as many psychosocial characteristics are fluid and at least partially modifiable. Based on this project's findings we intend to devise and trial appropriately focussed intervention programs that aid recovery and minimise long-term disabilities.Read moreRead less
Voltage Dependent Calcium Channels And Vascular Function: Do Microdomains Determine Function?
Funder
National Health and Medical Research Council
Funding Amount
$597,682.00
Summary
Blood flow depends on arterial diameter which can change with contraction of muscle in the vessel wall. Calcium influx through one type of channel in the muscle cells has been considered critical, but drugs targeting these channels have not succeeded in treating the arterial spasm which occurs after stroke and head injury. Our study will investigate the existence and role of other calcium channels in brain arteries. Knowledge gained will likely lead to development of new drug targets for stroke.
Hypoxia-inducible Factor-1 (HIF-1): Pharmacological And Molecular Insights Into Its Role In Brain Protection
Funder
National Health and Medical Research Council
Funding Amount
$293,229.00
Summary
At present, there are no effective therapies for reducing brain damage which can occur after acute brain insults including birth asphyxia. This project aims to study whether increasing a naturally occurring protective protein (HIF) in the brain can minimize brain damage in a model of perinatal brain injury. We plan to validate HIF as a novel therapeutic target for reduce brain injury and promote brain repair processes.
The Role Of Interferon Signalling In The Regulation Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
This project focuses on the role that inflammation plays in the progression of the type of neural injury seen in stroke victims. This project targets a specific pathway that is thought to be involved in the regulation of general inflammation but has not been greatly investigated in terms of the neural injury seen in stroke. Understanding the actions of this pathway may lead to future therapies that can be used to prime the brain to react in a positive way to stroke.
The Effect Of Smoking On The Exacerbation Of Stroke: Oxidative Stress Involvement And Cerebrovascular Response.
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
This grant addresses whether smoking contributes to the severity of stroke outcome. The studies outlined in this proposal will contribute significantly in our understanding of how smoking contributes to the progression of stroke. The understanding of the involvement of smoking in the progression of stroke will be of great benefit in the development of improved stroke patient management.
Towards A New Normokalemic Arrest Paradigm For Orthotopic Heart Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$489,634.00
Summary
Innovations from Nature to Heart Transplantation:a Real Heart Stopper Heart preservation is limited to 4-6 hours of cold-ischaemic storage (0 to 4 C). The risk of post-transplant death doubles if the donor heart is stored from 1 to 5 hours, and triples with 7 hrs storage times. We have developed a new preservation solution borrowing from natural hibernators that will permit organs to be safely stored for up to 15 hours, and offering new opportunities to organ donors and recipients worldwide.