Cell Death In The Retina: Analysing The Switch That Triggers Dependency On Target-derived Trophic Factors
Funder
National Health and Medical Research Council
Funding Amount
$428,414.00
Summary
Construction of the developing nervous system in the embryo involves the creation of nerve cells and their connections, but also involves loss of a proportion of these cells prior to maturation. We will study this process of cell death and how developing nerve cells switch on their dependency to survival factors. In so doing we will better understand what happens when brain development goes wrong and also devise new ways to protect nerve cells in the injured or degenerate adult nervous system.
What Is The Effect Of Alzheimer’s Disease On Eye And Can Ocular Changes Be Used As Biomarker For Alzheimer’s Disease?
Funder
National Health and Medical Research Council
Funding Amount
$718,002.00
Summary
Visual symptoms are frequent early complaints in Alzheimer’s (AD) patients. Examining eyes can be a simple, specific and inexpensive way to assess and diagnose AD and fill in an urgent need for a viable biomarker. Retina is unique part of central nervous system that can be imaged non-invasively and thus serves as a ‘window to the brain”. Monitoring the eyes will also help prevent negative effects of AD on vision by way of timely intervention, in addition to providing mechanistic insights in AD.
Is The Eye A Window To The Brain In Sanfilippo Syndrome?
Funder
National Health and Medical Research Council
Funding Amount
$852,967.00
Summary
Study of the retina and optic nerve permits evaluation of central nervous system – these structures contain both neurons and glia and are outgrowths of the developing brain. Therefore, eye examination may allow us to study the brain and monitor brain disease and the effect of therapy. This project will determine whether brain disease in a childhood-onset disorder (Sanfilippo syndrome) and treatment of it, can be monitored in this way.
Assessing The Efficacy Of Safe And Simple Neuroprotective Treatments For Chronic Degenerative Conditions Of The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Current treatments for age-related diseases of the central nervous system (CNS) are limited. We have shown in animal models of acute CNS degenerations that treatment with saffron or low energy infrared light is strongly protective. This project will determine if these treatments prevent CNS damage and dysfunction in animal models of chronic degenerations and add to knowledge of how these treatments work. This research should lay the foundation for testing these novel treatments in humans.
Central Nervous System Dendritic Cells – Guilty Or Not Guilty?
Funder
National Health and Medical Research Council
Funding Amount
$481,594.00
Summary
The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these b ....The central nervous system although structurally and functionally unique, must be able to mount protective immunological responses. However, breakdown in local and central immunoregulatory processes can lead to clinically disabling inflammatory conditions such as uveitis and multiple sclerosis. This project will investigate the role of Dendritic cells in models of autoimmune diseases affecting the eye and brain. The data will greatly aid our ability to design new immunotherapies to treat these blinding and crippling diseases.Read moreRead less
How Does Chronic Epilepsy Result In Cardiac Electrophysiological Dysfunction?
Funder
National Health and Medical Research Council
Funding Amount
$737,112.00
Summary
Cardiac dysfunction is common in epilepsy, and could be an important contributor to the increased risk of sudden death in people with epilepsy (SUDEP). In this grant we will investigate: when changes in the cardiac function develop in relation to the epilepsy; if people with chronic epilepsy have similar changes; and what effect seizures and epilepsy has on the nerves innervating the heart. The outcomes have the potential to motivate new treatments and prevention for this important problem.
Retinal Microvascular Signs In Acute Stroke: Prognostic Significance And Relevance To Underlying Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$375,425.00
Summary
This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that asses ....This project will describe abnormalities of the blood vessels of the retina in patients with stroke. Stroke is a common problem affecting some 48,000 Australians each year. Despite medical progress, stroke is commonly fatal (the third leading cause of death) and the leading cause of serious acquired disability in older people. This project will obtain detailed photographs of patients admitted to hospital with acute stroke. The acquired digital images will be analysed using new methods that assess size of the small retinal arteries compared to veins (the arteriole-to-venule ratio) and will document other abnormalities, such as microaneurysms, haemorrhages, tortuosity and focal and generalised vessel narrowing and wall opacity. In normal populations these signs are associated with hypertension, inflammation and endothelial dysfunction and predict future stroke. These signs, and their significance have not been systematically studied in acute stroke. This may offer a window into the brain for important subgroups of stroke such as lacunar stroke. It is increasingly hard (and remains technically very difficult) to study the cause of lacunar stroke, affecting 10,000 Australians each year, as lacunar stroke has a lower fatality rate (and thus few opportunities for post mortem studies) but a high disability rate. Lacunar stroke is known to be due to small vessel disease but the exact nature of this disease is unknown. Echocardiography (to identify heart and major blood vessel abnormalities) and carotid duplex scanning (to identify critical stenosis of the major blood supply to the brain) are commonly normal in this type of stroke, and brain scanning with computerised tomography (CT) or magnetic resonance (MR) merely shows the outcome of the small vessel disease. The eye develops as part of the brain and thus retinal vascular abnormalities could add important knowledge to our understanding of stroke and add clinically useful data in the assessment of patients with stroke.Read moreRead less
Optimising And Applying Ocular Vestibulat Evoked Myogenic Potentials (oVEMPs)
Funder
National Health and Medical Research Council
Funding Amount
$228,931.00
Summary
This project seeks to optimise techniques for a new method of assessing the balance organs (vestibular organs) and then apply these techniques. Three conditions will be studied: vestibular neuritis - a condition causing acute and severe dizziness; Parkinson's disease, in which disorders of balance are common and superior canal dehiscence (SCD) in which there is a hole in the bone overlying one of the semicircular canals, leading to sensitivity to sound.
Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw ....Improving Oral health is a priority of the NHMRC Strategic Plan 2003-06. The proposed research is consistent with this priority as we will achieve a better understanding of the cortical control of human jaw muscles, which serves as the foundation for understanding conditions in which their function is impaired, and the development of rational therapies for these conditions. Transcranial magnetic stimulation will be used to activate the motor cortex and corticobulbar descending pathway to the jaw muscles. The AIM 1 study will provide important new information about the functional organisation of the motor cortex in the control of jaw muscles during speech. This information is needed to improve understanding of dysarthria, a common disturbance of speech due to impaired muscular control following unilateral cortical stroke, and less common conditions involving speech motor control such as spasmodic dysphonia (a cranial dystonia) and dysprosody (disturbance of speech articulation and rhythm found in Parkinson s disease). The AIM 2 and 3 studies will provide a comprehensive characterization of cortical inhibitory mechanisms that are an important but poorly understood component of the cortical control of jaw muscles. This information is necessary to understand normal function, and the mechanisms of disturbances to jaw muscle function with neurological disease or injury. The AIM 4 studies will show whether impaired cortical inhibition contributes to the pathophysiology of two poorly understood disorders affecting jaw muscles (bruxism and oromandibular dystonia). Current therapies for these conditions are unsatisfactory, due to a limited understanding of the mechanisms involved. If cortical inhibition is abnormal in these conditions this will lead to novel treatment therapies (e.g., drugs to correct the imbalance, or strategies to induce plastic change in the cortex).Read moreRead less
Is EphA4 The Major Molecular Regulator Of Axonal Regeneration?
Funder
National Health and Medical Research Council
Funding Amount
$491,000.00
Summary
Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contri ....Spinal cord injury affects a substantial number of Australians each year. Around half the number of spinal cord injury cases result in quadriplegia, with loss of function to a varying degree in the upper as well as the lower limbs. The limited degree of repair of spinal axons following injury means that such paralysis is usually permanent. Although the inability to walk is a serious issue, the limited function of the arms and hands results in a loss of independence which is a major factor contribuing to the enormous personal, financial, and community costs of this problem, estimated to cost the Australian community $200 million a year. In recent years advanced anatomical and molecular approaches to the problem of repair of the central nervous system have provided great insights into the neuronal and glial reactions to neural damage that appear to govern the success or failure of neural regeneration. Our preliminary data indicate that a receptor tyrosine kinase, EphA4, which is important for axonal pathfinding in the developing nervous system, is a potent inhibitor of neural regeneration following spinal cord injury. In this project we will determine the mechanisms by which EphA4 exerts its inhibitory effects, and examine the effect of neutralizing EphA4 signalling on neural regeneration. Success in achieving this result will lead to the development of a therapeutic intervention that we will test in mouse models.Read moreRead less