Optimising Combinations Of Calcium Channel Inhibitors For Treatment Of Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$679,772.00
Summary
Traumatic injury to the central nervous system is made worse by damage that spreads away from the initial point of impact. Excess calcium entering cells is a key contributor to spreading damage but treatment with single calcium channel inhibitors has been disappointing. We will use combinations of calcium channel inhibitors to block multiple calcium channels and ensure the optimised combination is effective in clinically relevant models of neurotrauma.
Neuron To Glia Signalling: Learning How Synaptic Signalling Can Promote CNS Remyelination
Funder
National Health and Medical Research Council
Funding Amount
$609,650.00
Summary
An immature cell type in the brain, known as the oligodendrocytes progenitor cell (OPC), receives direct electrical communication from neurons. This communication regulates the behavior of the OPC, affecting its ability to divide and generate new brain cells. This project will identify the signaling molecules that guide the OPC to for this specialized contact with the nerve cell. Understanding this communication has important implications for the treatment of Multiple Sclerosis.
Targeted Nanoparticles To Deliver Combinations Of Calcium Channel Inhibitors To Prevent Myelin Damage During Secondary Degeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$895,244.00
Summary
Following injury to the central nervous system the damage spreads into nearby areas, leading to worse outcomes for the patient. We will generate nanoparticle systems to deliver effective therapies directly to the most vulnerable cells, critical for function. We will modify the nanoparticles so that they can get to the injury site, both early after injury, and after longer periods of time have elapsed. We will then test the nanoparticle systems to see if they are effective at preserving function
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.
Decoding Dysfunctional Spinal Cord Circuitry In Chronic Pain.
Funder
National Health and Medical Research Council
Funding Amount
$516,101.00
Summary
Chronic pain is common, with one in five Australians having long-term pain that is serious enough to cause disability. Unfortunately this type of pain is difficult to treat, and current medicines are ineffective in many people, with unwanted side-effects. The aim of this project is to understand how signalling in the spinal cord changes following the development of chronic pain so we can find better strategies to reverse the symptoms and treat pain more effectively.
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
The Role Of Action Potentials In Local Calcium Signalling And Induction Of Different Forms Of LTP
Funder
National Health and Medical Research Council
Funding Amount
$330,691.00
Summary
Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and ....Our understanding of how the brain learns and remembers things is still limited. There is good evidence that changing the strength of the connections (synapses) between brain cells (neurons) can allow information to be stored. One type of synaptic change is called long-term potentiaton (LTP), which is a long-lasting increase in the efficacy of communication between neurons. Recently, I have described 3 different forms of LTP in a region of the brain that is known to be important for learning and memory. These forms of LTP have different persistence characteristics - LTP 1 is relatively short-lasting, LTP 2 is of intermediate duration, and LTP 3 is very long-lasting and perhaps even permanent. Each form of LTP is selectively triggered by an increase in calcium in a different part of the neuron. In the present study, I will investigate the relationships between electrical activity in different parts of the neuron in order to define the 'rules' for triggering each form of LTP. This information is important for future studies into the specific role played by each form of LTP in learning and memory processing in the brain. A better understanding of the relationship between LTP and learning and memory will assist in developing effective treatment strategies for disorders of memory, including Alzheimer s disease, addictive bahaviour, and learning disorders.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.