The Role Of Interferon Gamma And Nitric Oxide As Downregulating Molecules In Central Nervous System Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$526,644.00
Summary
Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is rest ....Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is restricted only to a single model of CNS inflammation or is a general phenomenon within the CNS. The project will also involve a number of experiments designed to elucidate the mechanism(s) by which down regulation occurs. This project is highly significant in that a single uncontrolled clinical trial of interferon gamma for the therapy of MS has been carried out and reported as indicating that interferon gamma made the disease worse. The design of that trial however was such that the validity of that claim is questionable. If our experiments confirm the general nature of interferon gamma as a down regulator in inflammation in a number of different models of MS then a case for revisiting the use of interferon, or a downstream product of interferon, in the therapy of MS might be made.Read moreRead less
Inhibitors Of NLRP3 Activation For Treatment Of Inflammatory CNS Diseases
Funder
National Health and Medical Research Council
Funding Amount
$1,023,137.00
Summary
This project will use novel tool compounds to advance our understanding of inflammatory brain diseases such as Parkinson's disease and Multiple Sclerosis. We will examine the molecular pathways and identify novel means to treat these debilitating diseases. We will then aim to design novel therapeutics which target these pathways.
Encephalitis is a common cause of neurological disability in young adults and adolescents. We have identified a subgroup of encephalitis which is due to the patient's own immune system attacking the brain. Our study will identify the earliest immune responses against the brain in children with encephalitis. Identifying these early immune responses in people with encephalitis will allow early and directed treatments to prevent disability and death in the future.
I am a neuropharmacologist and a neuroanatomist who is involved in utilising a multidisciplinary approach to investigate the functional role of metalloproteinases in the brain.
Forebrain Neuroadaptations To Chronic Morphine Treatment
Funder
National Health and Medical Research Council
Funding Amount
$435,956.00
Summary
Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerv ....Drug addiction is caused by long term changes in brain areas that normally produce the drives that sustain normal behaviours such as eating, drinking and sex. Addictive drugs effectively hijack these brain areas so that behaviours relating to drug taking become associated with feeling good. In some individuals, over time the pattern of drug taking becomes compulsive and no longer can be controlled. This transition is now known to be due to drugs causing physical changes to certain groups of nerve cells in the brain. The affected nerve cells are responsible for causing new behaviours that appear once addiction is established. Addiction is not exclusive to humans. Animals will self-inject the same addictive drugs that humans use, and show many other kinds of addictive behaviours that parallel aspects of human addiction. Studying the effects of addictive drugs on rats and other animals has been very important in working out where and how drugs work. We now have a very good idea of which parts of the brain are affected by drugs, and it turns out that most addictive drugs act in the same places. We also now know for all of the major drugs, exactly which parts of nerve cells they affect. However, this turns out to be only the first step as the nerve cells that directly respond to drugs can affect other whole networks of nerve cells. This study is going to look at how morphine, a drug that is related to heroin, affects nerve cells in a part of the brain that helps cause addiction. It is going to work out which of the many pathways in this brain region are affected by morphine treatments that cause addiction in rats. It will then see what is happening to single nerve cells in the affected pathways. If we can understand more about these processes it may become possible to come up with new ways to treat addiction. We will also understand much more about the production of powerful emotional and behavioural drives so many of us find hard to control.Read moreRead less
Substance P Antagonists As A Novel Therapeutic Intervention In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and ....Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and subsequent brain damage in areas surrounding the central region of the stroke. These events develop over hours to days following the stroke and are known as secondary injury. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Nonetheless, few interventions are available that can limit this development. Our own recent studies have demonstrated that regions in brains which demonstrate the presence of stroke also exhibit signs of neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death in other tissues. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Thus, inhibiting substance P binding may offer a novel therapeutic approach to attenuating oedema formation and the development of neurologic deficits following stroke. This proposal will utilise a combined biochemical, pharmacologic and behavioural approach to characterize the role of neurogenic inflammation in the development of oedema and neurologic deficits following stroke. Moreover, we will develop a novel pharmacotherapy that can potentially be used in the treatment of clinical stroke.Read moreRead less
Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to und ....Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to understand the causal relationships between epilepsy and psychiatric disorders, and determine how and why psychiatric disorders and epilepsy co-exist. It is hoped that research conducted in this project will develop novel avenues to treatment of both epilepsy and psychiatric disorders.Read moreRead less