Establishing A Model Of Occlusive Middle Cerebral Artery Stroke In The Sheep
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Stroke is the second leading cause of death and the highest cause of disability in adult Australians, however our lack of an animal model that correctly replicates the human condition has severely hindered our understanding and treatment of the disease. This research project aims to develop a model of stroke in the sheep using a surgical approach that future researchers may use and adapt to further explore the physiology of the disease and trial therapeutic techniques to treat stroke.
The Sulphate Anion Protects Against Stroke: Characterisation Of Neuroprotective Potential And Mechanism Of Action.
Funder
National Health and Medical Research Council
Funding Amount
$189,170.00
Summary
Stroke-cerebral ischaemia affects approximately 40,000 - 50,000 Australians every year and is Australia's leading single cause of disability and second greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects approximately 40,000 - 50,000 Australians every year and is Australia's leading single cause of disability and second greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke to the Australian community is over $2 billion annually. Hence preventing or reducing brain damage following stroke is of fundamental clinical, social and economic significance. A stroke occurs when there is a reduced blood supply to the entire brain (Global ischaemia; eg. cardiac arrest, heart bypass surgery, closed head injury) or when there is a reduced blood supply to a specific region of the brain, usually as a result of a blockage in a brain artery (thrombo-embolic stroke or focal ischaemia). Despite decades of research, there is no totally satisfactory clinical treatment to reduce brain damage following stroke; the search for new treatments is paramount. We have shown that sodium sulphate can prevent brain damage in rat models of focal and global ischaemia. Importantly we demonstrated that sodium sulphate could prevent brain damage when given up to 8 hours after the stroke was induced in the global model. Delayed treatment following stroke is of clinical significance, since most patients do not receive medical attention until several hours after initial stroke symptoms. It is not known how sodium sulphate protects the brain from stroke. This project has three main aims: 1. To determine the how well sodium sulphate treatment protects the brain in rats following stroke. 2. To determine if sodium sulphate treatment can reduce brain damage in the rat model of focal ischaemia when given 4 - 8 hours after the stroke. 3. To determine how sodium sulphate protects the brain from stroke.Read moreRead less
Glial Reactivity During The Post-acute Phase Of Stroke: A Target For Promoting Functional Recovery
Funder
National Health and Medical Research Council
Funding Amount
$547,307.00
Summary
Recent studies suggest that the development of a type of scar around damaged tissue in the brain following a stroke can limit recovery. Our studies will improve understanding of events leading to scar formation and will test whether modifying these events can improve functional recovery in experimental stroke. The studies have excellent potential to identify targets for treatments that will reduce the long-term debilitating effects of stroke even when administered well after its onset.
Stroke is a devastating disease causing mortality and morbidity on a massive scale, and which still has no treatment besides a clot-buster that cannot be used in 90% of patients. This research should provide a better understanding of stroke pathology and identify new therapeutic directions. It will elucidate an unappreciated but crucial role of specific immune cells in brain injury after stroke, and hopefully lead to new ways to limit brain injury and promote recovery from stroke.
Evaluation Of Combined Mild Hypothermia And Magnesium As A Neuroprotective Therapy Following Cerebral Ischaemia/stroke
Funder
National Health and Medical Research Council
Funding Amount
$310,286.00
Summary
Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.Read moreRead less
This proposal seeks to determine the therapeutic potential of stem cells for the treatment of brain injury early in life, for example as occurs in cerebral palsy. The project will test the capacity of implanted stem cells to both protect the brain and also to functionally replace cells lost to the injury in order to improve motor and cognitive function.
This project will test whether activators of a novel estrogen receptor (GPER) can limit brain injury and functional deficits after stroke in mice. Part of the work will evaluate two drugs currently in clinical use for chronic conditions – tamoxifen and estradiol – as potential therapies for use in acute stroke. We will study the therapeutic time window of several drugs over up to a week after stroke, and identify key mechanisms underlying the protection by these GPER drugs.