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.
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
An inability to resist a temptation or repeated failures of self-regulation can lead to 'impulsive' and 'compulsive' behaviours that relate to a host of personal and social problems (eg., excessive eating, gambling, and substance use). Despite this, very little research has studied the neural and psychological underpinnings of these behaviours. My research will take advantage of recent innovations and approaches to fill this void and have implications for diagnosis and treatment.
Evaluation Of Combined Mild Hypothermia And Magnesium As A Neuroprotective Therapy Following Cerebral Ischaemia/stroke
Funder
National Health and Medical Research Council
Funding Amount
$310,286.00
Summary
Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.Read moreRead less