Roles Of Peripherally Derived BDNF In Regeneration Of Spinal Cord And The Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful complet ....Injury to the brain and spinal cord often leads to permanent disability due to lack of regeneration. The mechanism why central nerve does not regenerate is not known. Neurotrophic factors are powerful molecules which can overcome effects of inhibitory factors on regeneration. This project aims to investigate how neurotrophic factors override the effects of inhibitory factors and how to improve the regeneration by increasing the production of neurotrophic factors within nerves. Successful completion of this project will help understanding the mechanism of how neurotrophic factors work on regeneration and developing the effective way to improve regeneration of the injured spinal cord.Read moreRead less
Viral-mediated Modulation Of BDNF Expression In Motor Neurons To Promote The Recovery Of Hand/digits Function In A Rat Model Of Spinal Cord Injury That Impairs Normal Grasping Action.
Funder
National Health and Medical Research Council
Funding Amount
$341,427.00
Summary
This project seeks to lure injured axons towards motor neurons, a process that is essential for the recovery of motor function. BDNF gradients will be created along the injured axons path. Axons will have to elongate to reach the first source of BDNF. They will need to elongate even more to get to the next source of BDNF, hence bringing them each time closer to their lost targets. This gene therapy scenario has the potential to bring gene therapy a step closer for human spinal cord injury.
Functional Neurogenesis In The Injured Neocortex Of The Nonhuman Primate
Funder
National Health and Medical Research Council
Funding Amount
$966,048.00
Summary
Research over the past couple of decades has revolutionised our understanding of the capacity of the brain to generate new cells, especially following an injury. However, what does remain controversial is whether this phenomenon occurs in all areas of the brain, especially following a severe traumatic brain injury or stroke. This project will examine whether the outer surface of the brain has the potential to generate new cells following a brain injury and whether they become functional.
The Final Common Channel: Measurement Of Nerve Excitability In Epilepsy.
Funder
National Health and Medical Research Council
Funding Amount
$301,376.00
Summary
Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of ....Epilepsy may be due to either one single genetic mutation or a combination of several gene-environment interactions, affecting how ion channels function. It is not possible to directly interrogate channels in the living human brain but, because similar channels are found in peripheral nerve, much may be learned about aberrant channel function from peripheral nerve. This project aims to measure peripheral nerve excitability in epilepsy patients, using it as a marker of the final common pathway of channel dysfunction.Read moreRead less
The Combined Use Of Transplantation And Gene Therapy Techniques To Promote Regeneration After Neurotrauma
Funder
National Health and Medical Research Council
Funding Amount
$521,026.00
Summary
Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce gen ....Trauma in the adult mammalian central nervous system causes long-lasting functional deficits. The resulting physical and financial burdens to the individual, to his or her family, and to the community at large, are immense. When fibre tracts are damaged there is disruption of circuits and there may be death of associated nerve cells. Interventions are therefore necessary to promote repair and to try to restore function. Highly modified, non-harmful viruses can be used as vectors to introduce genes into cells, a method that allows targeted supply of molecules to the injured brain. Gene and cell therapy may eventually be of clinical benefit to injured patients. In a range of different experiments we will combine two different gene therapy approaches, various pharmacological agents and novel transplantation strategies in attempts to enhance the survival of affected nerve cells and promote the regrowth of damaged nerve fibres across injury sites in the injured adult rat visual system. Long-term vector-mediated expression of growth factors in neurons and in grafts may 'trap' regenerating axons, potentially reducing their outgrowth into distal, denervated target areas. It is therefore important to determine if temporal regulation of growth-promoting genes has additional beneficial effects on the ability of regenerating neurons to recognise and selectively regrow axons into appropriate CNS targets. An additional series of studies will thus be undertaken. We will test a new generation of regulatory vectors in which it is possible to switch the virally encoded genes on or off and thus control the level and timing of gene expression over a therapeutic range. We will then determine if the use of these regulatory viral vectors results in more consistent and robust growth of nerve fibres with better reconnections, in the longer term leading to better recovery of function.Read moreRead less
We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being pas ....We are able to identify and discriminate objects in the world because of exquisitely detailed and rapid processing of sensory information by neurons in the cortex of the brain. In this project we will examine these operations in neurons in the cortex that receive input from the large face whiskers of the rat. These whiskers are used for fine-grain discrimination and for gauging distance. They are deflected by being actively moved, under muscle control, over objects (active touch) or by being passively deflected by objects. Deflection results in inputs to the brain that are processed to form the neural basis for very finely detailed perceptual behaviour. In rats, with impoverished visual and auditory senses, the whiskers are the major sensory system for interacting with the world, and are used in navigating the environment and in finding and distinguishing foods. Thus they contribute strongly to the remarkable success of this species. This elegant sensory system has a number of advantages that make it a very good model for the study of brain mechanisms responsible for active fine-grain sensory function. We plan to take advantage of the unique features of this system to define the information processing that occurs in the cortex in this elegantly complex system. This will address an issue relevant to all sensory systems - namely the neural basis of complex fine grain perceptual behaviour. Understanding the mechanisms underlying active tactile perception also has relevance to clinical conditions involving deficits in active touch e.g., in diabetic polyneuropathy (which eventually affects ~50% of diabetics), in leprosy (in which an early sign is damage to active touch). Knowledge of the core brain processes in active touch gained in this study could eventually underpin the ameliorative technologies for such deficits.Read moreRead less
Computational Analysis Of The Influence Of Growth Cone Shape Dynamics On Axon Guidance
Funder
National Health and Medical Research Council
Funding Amount
$346,406.00
Summary
For the brain to function correctly its neurons must be connected correctly. This project will use a novel mathematical approach to understand how growing nerve fibres find where to go in the developing brain. In particular we will use both experiments and computational analysis to understand how the shape of the tip of a growing nerve fibre helps the fibre navigate. This may help us understand the biological cause of many different types of mental disorders.
Development Of Pthaladyn-based Dynamin I-selective Inhibitors For Treatment Of Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$564,310.00
Summary
About 1% of the World�s population suffers from epilepsy; 30% fail to respond to anti-epileptic drugs (AED). Current AED development pathways have changed little in the past 20 years with the majority of current AEDs dampening the release of crucial chemical signals 24/7. Our new drugs, which inhibit a protein called dynamin, are only recruited at the onset of a seizure. Our approach will significantly enhance the day to day lives of those afflicted by epilepsy.