The Role Of Gas6 And The TAM Receptors In Central Demyelination
Funder
National Health and Medical Research Council
Funding Amount
$506,416.00
Summary
In Multiple Sclerosis, oligodendrocytes, the myelin-producing cells of the brain, are damaged and myelin is lost in a process called demyelination. This process also involves the brain's immune cells, called microglia. Both cell types are influenced by a factor called Gas6, which signals through proteins called Tyro3, Axl and Mer. We have shown that levels of Gas6 can affect the severity of demyelination in mice. We plan to further study the effects of these proteins during demyelination.
Novel Radiolabelled Peripheral Benzodiazepine Receptor (PBR) Ligands For Imaging And Treating Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$425,460.00
Summary
Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destructio ....Neuroinflammation is involved in chronic, slowly progressive neurodegenerative diseases such as Multiple Sclerosis, and Alzheimer's, Parkinson's and Huntington's Diseases. A signifiacnt and early charactersitic in the development of neuroinflammation and the progression of these diseases is the damaging changes that occur to specific cells called glial cells in the brain. Termed microglial activation these changes cause regions of the brain to succumb to progressive disease and tissue destruction. The ability to pickup early signs of injury or to measure destructive changes to glial cells in the brain using noninvasive imaging techniques would be of great value in the clinical diagnosis and management of neurodegenerative disease. The ubiquitous nature of these activated microglia also makes the microglia a target for the development of pharmacological approaches to the treatment or prevention of many central nervous system diseases. Researchers at ANSTO and the ANU have developed a novel class of molecules, which target a specific protein called the peripheral benzodiazepine receptor or PBR which is enhanced in damaged glia. Radiolabelled analogues of these molecules have demonstrated a strong correlation between inflammation and the expression of this receptor in various animal models of inflammation and neurodegeneration. Furthermore, these molecules have the potential to inhibit further damage to these glial cells and could potentially slow down the progression of the disease. Therefore, further development of these molecules both as radiopharmaceuticals for noninvasive medical imaging and-or as inhibitors of microglial activation could have a significant impact on the understanding, management and treatment of neurodegenerative disease.Read moreRead less
This project aims to investigate novel ways to treat children with the inherited brain disorder known as MPS IIIA. This condition is currently untreatable and children generally die in their teens. We will use a mouse model of this condition to examine the effectiveness of combining two different treatment approaches, in order to maximise outcomes.
REVERSIBLE AND IRREVERSIBLE TNF-MEDIATED COGNITIVE DECLINE
Funder
National Health and Medical Research Council
Funding Amount
$444,460.00
Summary
This proposal seeks to clarify the neuronal mechanisms underlying the inflammatory processing leading to cognitive decline. Furthermore, the research project identifies anti-inflammatory treatment options aiming at improved cognitive performance in people at risk for or suffering from cognitive impairment of neuropsychiatric disorders such as dementia and depression.
The Role Of Proinflammatory Interleukin-17 (IL-17) And IL-17-producing T Cells In Neuropathic Pain
Funder
National Health and Medical Research Council
Funding Amount
$470,051.00
Summary
Peripheral nerve injury often results in persistent and debilitating neuropathic pain. My overall objective is to understand the immunological mechanisms responsible for such pain. I plan to test the hypothesis that the proinflammatory cytokine interleukin-17 promotes neuroinflammation and contributes to increased pain sensitivity after nerve injury. This study promises to enhance our understanding of neuroimmune activation in neuropathic pain and offers new opportunities for pain management.
Astrocytic Glutamate Transporters: Molecular Characteristics Of Their Activity-dependent Localization And Targeting
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
Dysfunction of glutamate transport is implicated in the pathology of neurodegenerative conditions. Our aim is to understand how the molecules responsible for glutamate transport are organized on the cell surface and how their movement within cells regulates transporter activity. Advances of this type will indicate new pharmacological and molecular biological strategies for the management of brain disorders.
Immunopathological Role Of Monocyte-macrophages In Flavivirus Encephalitis.
Funder
National Health and Medical Research Council
Funding Amount
$445,011.00
Summary
Viral encephalitis is a life-threatening infection of the brain for which there are no reliable treatments. White cells called monocytes enter the brain from the blood and although important in the immune response that destroys the virus, can also damage the brain. Our work focuses on determining how monocytes migrate into the brain in viral infection, what functions they have once inside the brain, and how to exclude a certain types of monocytes that we have found to be particularly damaging.
Role Of Post-traumatic Hypoxia In The Exacerbation Of Cerebral Inflammatory Response Elicited By Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$397,535.00
Summary
Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) a ....Traumatic brain injury is the major cause of death in the young population below the age of 40 years. Approximately 25% of patients that survive head injury remain with permanent neurological disabilities with considerable family, professional and economic costs. Extensive research has shown that not all brain damage occurs at the time of injury, but rather evolves over the hours and days following trauma. Secondary injury may result from various factors including hypoxia (insufficient oxygen) as a consequence of respiratory distress that occurs in about 50% of patients with severe head trauma. Hypoxia is known to significantly worsen the neurological impairment and potentially lead to death. Brain injury and hypoxia have the ability to separately trigger cerebral inflammation. A dual role has been attributed to inflammation: to promote tissue repair but also add further damage through the release of neurotoxic substances. We hypothesise that hypoxia occurring after traumatic brain injury enhances the inflammatory response in the brain and aggravate tissue damage as well as neurological dysfunction. This hypothesis will be tested on a rat model of brain injury whereby the animals will be exposed to moderate-severe hypoxia immediately after trauma. The production of multiple inflammatory mediators will be quantified in the brain tissue and also in cerebrospinal fluid. The concentration of these mediators will be compared with the levels of cellular injury proteins known to increase following injury to determine whether a correlation exists. In a clinical study on patients, we will measure the same inflammatory mediators and proteins in the cerebrospinal fluid and blood of individuals with severe head injury. The suitability of these factors for potential use as diagnostic-prognostic markers of either hypoxia or injury will be determined.Read moreRead less
The Kynurenine Pathway Chemokines And MIC-1 In The Pathogenesis Of AIDS Dementia Complex.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
This proposal will examine the mechanisms by which HIV and other brain disorders such as encephalitis damage the brain. Further understanding of the biochemical pathway involved will lead to the possibility of novel drug therapy for these disorders.
The Role Of Interferon Signalling In The Regulation Of Stroke
Funder
National Health and Medical Research Council
Funding Amount
$620,381.00
Summary
This project focuses on the role that inflammation plays in the progression of the type of neural injury seen in stroke victims. This project targets a specific pathway that is thought to be involved in the regulation of general inflammation but has not been greatly investigated in terms of the neural injury seen in stroke. Understanding the actions of this pathway may lead to future therapies that can be used to prime the brain to react in a positive way to stroke.