Improving Clinical Translation In Stroke: Targeting Cerebral Oedema In A Large Animal Model
Funder
National Health and Medical Research Council
Funding Amount
$637,530.00
Summary
A common and life-threatening complication of stroke is brain swelling which is the leading cause of death within one week of stroke and a predictor of poor outcome. Current treatments for brain swelling are inadequate. We have developed a drug that blocks the action of the neuropeptide substance P, which is involved in the development of swelling. We will assess the efficacy of this treatment to reduce brain swelling and improve long-term outcome in a relevant pre-clinical model of stroke.
Neuroscience On Barriers In Development (NEUROBID)
Funder
National Health and Medical Research Council
Funding Amount
$600,927.00
Summary
The program aims to understand normal and disturbed brain barrier function in development to devise ways of preventing or ameliorating neurological conditions in infants or adult neurological disorders with developmental origins. Unique features of transport mechanisms across brain barriers will be used to design novel methods of targeting therapeutic macromolecular and cellular agents to the brain barriers and transporting them into brain for treatment of neurological diseases in young and old.
Targeted Delivery Of CD39 To Ischaemic Brain Improves Outcomes In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$895,780.00
Summary
Stroke is most likely caused by a clot in one of the large blood vessels supplying the brain. The approach is to save the 'at-risk' area of brain with drugs that break-down clots and by manual removal of clots. These treatments are limited by timely access within 4.5 hours to larger hospitals. We are trialing a new drug that protects the brain better on its own and may add to the benefit of current treatments. Moreover, it can be given in any rural setting.
Spinal cord cysts can develop after spinal injury or in association with tumours or congenital abnormalities of the spine. These cysts often cause pain and paralysis. Treatment is often ineffective, partly because the source of the cyst fluid is unknown. We are investigating the origin of this fluid using animal models of spinal cord cysts, computer simulations, and MRI studies of patients with spinal cord cysts. Understanding the origin of cyst fluid will help us to develop improved treatment.
Exploring Scanning Ultrasound (SUS), A Novel Method To Treat And Prevent Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$765,708.00
Summary
We developed a novel scanning ultrasound (SUS) protocol that clears toxic protein aggregates and restores memory function in mouse models of Alzheimer's disease (AD), without the need for therapeutic agents. Here we aim to determine whether SUS has preventative potential, whether there are synergistic effects, and whether a therapeutic antibody combined with SUS leads to an enhanced therapeutic outcome. Together this will guide the development of an ultrasound therapy in AD patients.
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
To Understand The Role Of The Plasminogen Activating And Matrix Metalloproteinase Systems In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$499,321.00
Summary
Tissue-type plasminogen activator (t-PA) is known for its role as a clot dissolving protein. It is present in the brain and following traumatic brain injury (TBI), it can worse brain cell damage. We have established a mouse model of TBI . We will compare brain damage in mice that are deficient in or have high amounts of t-PA. We will also determine whether the recovery rate post-TBI can be improved using specific t-PA blockers. This project may provide new therapies for TBI.
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Prof Alan Connelly is an internationally recognised neuroimaging researcher specialising in MRI. His major areas of research are in the development of new methods to acquire and process MR images of both structural and functional aspects of the brain, and the application of these novel methods to clinical neuroscience problems. His work has had a major impact in the field of epilepsy, where techniques that he pioneered have been widely adopted in specialist epilepsy centres worldwide.
Mild traumatic brain injury (TBI) is a leading cause of death and disability in Australia, especially in young populations. Although many patients recover uneventfully following mild TBI, complications such as prolonged symptoms, depression and cognitive deterioration may occur. With considerable advancements in neuroimaging and cognitive assessment in recent years, newer techniques may provide a window to directly observe changes that accompany mild TBI.