Acute Stroke: Imaging The Ischaemic Penumbra With Perfusion CT
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressivel ....The burden of stroke is large. Clot-dissolving medication (thrombolysis) may dramatically improve the outcome of many patients with severe stroke by unblocking the affected brain artery. However, very few patients receive this medication, as the current approval is restricted to treatment within 3 hours of stroke onset. The major aim of thrombolysis is to rescue brain tissue with reduced blood flow (the ischaemic penumbra) from becoming irreversibly damaged (infarcted). The penumbra progressively becomes infarcted over the next 48 hours if blood flow is not restored by the blood clot in the brain artery being dissolved. Penumbral brain tissue cannot be identified with clinical assessment or standard CT scanning. New generation CT scanners are capable of assessing brain blood flow. Perfusion CT imaging (CTP) is well tolerated and time-efficient, and can be integrated into the brain CT scanning process performed on all stroke patients. Preliminary evidence suggests that CTP can distinguish between tissue that represents the ischaemic penumbra, and tissue that is already permanently injured. This project aims to validate the use of CTP in imaging the ischaemic penumbra. This will be based on testing the accuracy of CTP tissue signatures of the penumbra in predicting clinical outcome and final stroke size. This is the only national collaborative study planned worldwide for this relatively new but increasingly accessible imaging technique. The ability to rapidly identify under-perfused but still viable brain with CTP would add new and exciting management options to the routine emergency assessment of stroke patients. The results of this unique study could have a significant impact on the management of acute stroke worldwide. If validated, it is anticipated that CTP would be widely used to improve patient selection for stroke thrombolysis, especially in safely extending the time window so that a greater number of patients can be treated with better outcomes.Read moreRead less
Low-Dose Tenecteplase Vs Standard-Dose Alteplase For Acute Ischaemic Stroke: An Imaging Based Safety And Efficacy Study
Funder
National Health and Medical Research Council
Funding Amount
$349,281.00
Summary
This study compares standard dose alteplase (a proven stroke thrombolytic) with a low dose of the new medication tenecteplase for stroke treatment. We propose that the clot-dissolving activity of low-dose tenecteplase will be superior to alteplase, with a lower risk of brain bleeding. MRI scanning is the most effective way of assessing outcomes and will be used to measure how well the medication restores blood flow, the amount of permanent brain damage, and whether any brain bleeding occurs.
To Investigate How The Aggregation Of Proteins During Neuronal Injury Promotes Neurotoxic Plasmin Formation
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
tPA is an enzyme given to patients to remove stroke-causing blood clots but can have harmful effects in the brain. tPA needs a cofactor to function optimally. In the blood, this cofactor is fibrin. However the cofactor that allows tPA to function in the brain is unknown. This project explores a novel cofactor for tPA in the injured brain. We will attempt to block this harmful cofactor in the brain while still allowing tPA to remove clots thereby improving stroke outcome.
To Determine The Means By Which Plasminogen Activators Modulate Integrity Of The Blood Brain Barrier
Funder
National Health and Medical Research Council
Funding Amount
$523,084.00
Summary
Tissue-type plasminogen activator (t-PA) is used clinically to remove blood clots. However, t-PA can also cause brain injury and influence the blood brain barrier (BBB) which has implications for the treatment of patients with ischaemic stroke. This project will use in vitro and in vivo models to understand the mechanism by which t-PA modulates the BBB. A novel tPA variant will also be created that ultimately may be of benefit for patients with ischaemic stroke.
The Adverse Effects Of Diabetes On Stroke: An Echoplanar MRI Study
Funder
National Health and Medical Research Council
Funding Amount
$278,418.00
Summary
Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncer ....Stroke is the most common, major brain disease in Australia. It is the third most common cause of death and the most common cause of adult disability. There is a close link between diabetes and stroke. Firstly, diabetes is an important risk factor for the development of stroke. Secondly, about one third of stroke patients have diabetes. In general, their outcome is much worse than other patients. In fact little is known about the cause of this adverse effect in stroke patients and there is uncertainty whether intensive control of blood sugar in acute stroke improves outcome. Our pilot work suggests that raised brain lactate, together with larger stroke size, might together be responsible for the worse outcome in diabetic patients. We can now measure brain lactate and stroke size with new MRI techniques called echoplanar MRI, which can allow measurements of brain chemistry, blood flow, potentially viable and dead tissue. A new monitoring device allows non-invasive measurement of blood sugar every 5 minutes. Using these strategies, we are planning a comprehensive study of the causes of the worse stroke outcome with diabetes. In addition, we are incorporating a study to determine whether intensive control of blood sugar in the first 3 days after stroke, compared with standard treatment, reduces brain lactate and growth of the actual stroke. An understanding of these effects will have important implications for the acute treatment of stroke patients. If we can show that rigorous control of blood sugar reduces brain lactate and stroke growth, our study will lay the ground work for a large clinical trial. This could have important implications, both in Australia, and overseas.Read moreRead less
INTERACT: A Randomised Trial Of Intensive Blood Pressure Lowering In Acute Intracerebral Haemorrhage
Funder
National Health and Medical Research Council
Funding Amount
$2,680,868.00
Summary
Intracerebral haemorrhage (ICH) is a serious type of stroke affecting thousands of Australians and 2-3 million people in the world each year, with most either dying or left disabled. There is no proven treatment for ICH, although surgery is sometimes used and early injection of a special clotting factor may improve outcome. One potential simple therapy is the rapid control of elevated blood pressure (BP) which occurs commonly and predicts a poor outcome in ICH, possibly by increasing bleeding an ....Intracerebral haemorrhage (ICH) is a serious type of stroke affecting thousands of Australians and 2-3 million people in the world each year, with most either dying or left disabled. There is no proven treatment for ICH, although surgery is sometimes used and early injection of a special clotting factor may improve outcome. One potential simple therapy is the rapid control of elevated blood pressure (BP) which occurs commonly and predicts a poor outcome in ICH, possibly by increasing bleeding and swelling in the brain. There is much uncertainty as to the optimal management of elevated BP in ICH. This study, called INTERACT, aims to determine the balance of benefits and risks of a management strategy of early rapid BP lowering in 2000 patients with ICH randomised from 100 clinical sites in Australia-Asia.Read moreRead less
TNF Traffic And Secretion In Astrocytes And Microglial Cells: Unveilling New Targets For Ischemic Stroke
Funder
National Health and Medical Research Council
Funding Amount
$585,070.00
Summary
Neurodegenerative disorders share a similar pathway to disastrous neurotoxicity, which occurs through the release of cytokines such as tumour necrosis factor-a (TNF) from glial cells. TNF controls inflammation but its excessive secretion in the brain is highly detrimental. The mechanism of TNF secretion is unknown but strategies aimed at reducing it have therapeutic potential. This grant proposes to study TNF discharge to find new ways to reduce secretion and confer protection in a stroke model.
Preventing Myocardial Infarction: A Mouse Model Of Atherosclerotic Plaque Instability/rupture As Unique Tool For Establishing Novel Pharmacological Strategies And Targeted Molecular Imaging
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarctio ....Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarction.Read moreRead less
Improving Outcome After Stroke: A Large, Multicentre, Randomised Controlled Trial Of Very Early Mobilisation (AVERT)
Funder
National Health and Medical Research Council
Funding Amount
$2,915,758.00
Summary
In Australia, stroke accounts for 25% of all chronic disability. The personal and community burden of stroke-related disability is likely to increase considerably over the next 20 years, as the population ages. Without effective prevention and treatment strategies, stroke-related disability and its associated costs will increase. For treatments to have any major impact on death or dependency, they must be widely accessible, cost-effective, appropriate, safe and effective in the vast majority of ....In Australia, stroke accounts for 25% of all chronic disability. The personal and community burden of stroke-related disability is likely to increase considerably over the next 20 years, as the population ages. Without effective prevention and treatment strategies, stroke-related disability and its associated costs will increase. For treatments to have any major impact on death or dependency, they must be widely accessible, cost-effective, appropriate, safe and effective in the vast majority of patients. There is preliminary evidence from Norway that patients who start mobilising (i.e. sitting out of bed, standing and walking) within 24 hours of stroke are more likely to be discharged home (rather than require long term nursing home care), have a shorter stay in hospital, and improved outcome compared to patients who receive general medical ward care. This intervention is simple and more widely applicable than many other acute interventions, but it requires testing. We will conduct the first randomised controlled trial of very early mobilisation after stroke to determine the cost and benefits of the intervention. Patients will be randomised to receive either standard care or standard care in addition to very early and frequent mobilisation. At 3 months post stroke, we will identify the number of patients dead and disabled in each group to determine the effect of intervention on outcome. We will also determine care costs and quality of life in the longer term. The trial design enables comparisons to other standard interventions to improve stroke outcome to be made. We have already recruited two sites and randomised 46 patients to the pilot study. No safety or feasibility concerns have been raised. If positive, this study has the potential to lead to significant changes in clinical practice that may serve to reduce the burden of stroke to both individuals and the broader community.Read moreRead less