Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
Acute Stroke Care: Rapid Unblocking Of Vessels, Mending Ruptures, And Recovery
Funder
National Health and Medical Research Council
Funding Amount
$204,399.00
Summary
During this fellowship, A/Prof Meretoja will 1) use blood biomarkers, telemedicine, and ambulance-based imaging to streamline the time-critical therapy of stroke thrombolysis, 2) run a pharmaceutical trial of the drug tranexamic acid in intracerebral haemorrhage, and 3) use stroke registries in Australia and Finland to disseminate best practices in stroke care pathways.
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
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
Stroke outcomes directly relate to brain tissue rescue. We have contributed to changes in clinical practice through many clinical trials of new protocols and therapeutic strategies. Our program will focus on brain salvage in the pre-hospital setting and the acute hospital environment. We will use novel approaches to enhance brain recovery and design new implementation strategies to maximise the benefits of these therapeutic advances.
I am a practising hospital neurologist and world leader in the prevention and treatment of stroke. Our research aims to realise exciting new break-throughs for stroke sufferers by testing the effectiveness and safety of new treatments that promise to improve recovery of function of damaged brain and reduce disability after stroke, and to prevent recurrent strokes.
Post-stroke Hyperglycaemia – Treatment With Exenatide In Acute Ischaemic Stroke (TEXAIS) Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,266,149.00
Summary
Raised blood glucose levels (hyperglycaemia) after a stroke is common. It reduces the efficacy of stroke treatments and results in worse outcomes. Insulin is not useful as a treatment for this as it causes frequent hypoglycaemia and does not improve clinical outcomes. Exenatide is a common diabetes drug that is simple to use and lowers blood glucose without hypoglycaemia. It will be tested in the Treatment with Exenatide in Acute Ischaemic Stroke (TEXAIS) trial.
An Australasian, Multi-centre, Randomized, Double-blind, Placebo-controlled Trial Of The Efficacy Of Fluoxetine In Improving Functional Recovery After Acute Stroke
Funder
National Health and Medical Research Council
Funding Amount
$2,306,367.00
Summary
Stroke is one of the top three causes of disability. Treatments that improve recovery after stroke are lacking. We reviewed the world literature and found a number of very small studies which, together, suggest that the antidepressant drug, fluoxetine, may improve the recovery in stroke patients. AFFINITY is a large trial in 1600 Australians and New Zealanders with stroke which aims to find out whether taking fluoxetine for 6 months after a stroke improves recovery compared to a placebo.
Stroke is a major cause of death and disability in adult across the world. Understanding how exactly brain cells are affected in stroke and how they are injured, and how they response to treatment is important in order to develop new treatment to maximize recovery and minimize brain injury after stroke. This project uses advanced MRI being performed at several time points after a stroke to study how the brain tissues recovers or dies after a stroke.
Centre For Research Excellence In Stroke Rehabilitation And Brain Recovery
Funder
National Health and Medical Research Council
Funding Amount
$2,595,746.00
Summary
The Centre of Research Excellence in Stroke Rehabilitation and Brain Recovery will transform the stroke research and practice landscape in Australia, and accelerate the development of new interventions strongly supported by neuroscience. This unique collaboration will improve patient selection and rehabilitation research methods, create a training culture for the next generation of rehabilitation researchers and effectively implement proven cost effective interventions for Australians.