COMBIT: Randomised Controlled Trial Of Novel Upper Neurorehabilitation For Congenital Hemiplegia
Funder
National Health and Medical Research Council
Funding Amount
$486,588.00
Summary
Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of t ....Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of the intervention.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.
Cerebral Palsy is most common childhood physical disability. While the brain injury is static, disability can be progressive and lifelong. This fellowship aims to develop and test novel interventions to optimise neuroplasticity by improving early detection and physical, cognitive, psychological and health outcomes in children with CP. Earlier accurate detection of CP will ensure effective treatments utilise critical periods of brain development and are translated into evidence based guidelines.
Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.Read moreRead less
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.
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.
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 Claustrum Enigma: Unlocking The Role Of The Last Unknown Area Of The Primate Brain
Funder
National Health and Medical Research Council
Funding Amount
$558,364.00
Summary
Despite nearly 200 years of study, the function of the claustrum remains unclear. Interest in this brain structure has recently been revived by findings showing damage to the claustrum in several major diseases, and by the suggestion that the claustrum may have a role in consciousness. Here we propose a series of experiments to test the novel hypothesis that the claustrum is part of the default mode network, a group of brain areas that act together when we aren't thinking about anything in parti ....Despite nearly 200 years of study, the function of the claustrum remains unclear. Interest in this brain structure has recently been revived by findings showing damage to the claustrum in several major diseases, and by the suggestion that the claustrum may have a role in consciousness. Here we propose a series of experiments to test the novel hypothesis that the claustrum is part of the default mode network, a group of brain areas that act together when we aren't thinking about anything in particular, that is- most of the time.Read moreRead less
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
Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.