Functional MRI And MR Spectroscopic Studies Of Penicillin Induced And Kindled Sheep Models Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$311,244.00
Summary
Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new techni ....Epilepsy is one of the most common neurological disorders, affecting 1-2% of the population. Many epilepsy patients do not respond to drug therapy and their only hope for seizure control is surgical removal of the part of the brain responsible for their seizures. Successful surgery is very much dependent on the ability to exactly localize the seizure focus and this is often not possible using the imaging techniques currently available. Functional magnetic resonance imaging (fMRI) is a new technique which may improve our ability to localize the seizure focus from which seizures arise, if the brain can be imaged at, or near, the time of a seizure. MR spectroscopy (MRS) enables us to detect metabolic changes in the brain which may persist at the site where seizures have begun for up to 30 minutes after the seizure. The aim of our research is to obtain a greater understanding of the changes detected with these MR modalities so that we can learn to apply these techniques to human sufferers of epilepsy. Ultimately it may help enable previously incurable epilepsy patients to undergo successful surgery and live normal lives.Read moreRead less
Magnetic Seizure Therapy:The Neural Correlates And Neurocognitive Outcomes Of A Novel Therapeutic Approach To Depression
Funder
National Health and Medical Research Council
Funding Amount
$231,147.00
Summary
Depression is a substantial clinical problem for which ECT is the most efficacious treatment. However, ECT has cognitive side-effects which limit its applicability and acceptance by patients. The development of a new treatment with similar efficacy but which minimizes these side effects would have great clinical value. One promising possibility is magnetic seizure therapy (MST). This project will investigate the neurological outcomes of MST in depression, focusing on the cognitive outcomes.
Neourobiology Of Human Epilepsy: Genes, Cellular Mechanisms,network And Whole Brain
Funder
National Health and Medical Research Council
Funding Amount
$17,652,824.00
Summary
The team is comprised of neurologists, molecular geneticists, physiologists and brain imaging specialists and leads the world in the discovery of the genetic causes of epilepsy. They will continue to identify genes underlying epilepsy and study how genetic variations result in development of seizures. Advanced brain imaging will be used to understand the effects of genetic variation on brain structure and function. This study may lead to new diagnostic methods and treatments for epilepsy.
How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
Cellular And Molecular Determinants Of Preleukaemic And Leukaemic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$292,635.00
Summary
It has recently become evident that the formation, growth and relapse of many cancers is driven by a rare population of cancer stem cells (CSCs) that have the unique ability to propagate new tumours and are highly resistant to current therapies. However, which normal cells are transformed into CSCs is not known. We will take a potent cancer gene found in leukaemia, and switch it on and off in specific blood cells in mice to determine which healthy cells can be turned into leukaemic stem cells.