Hypothermia Prior To Decompression For Treatment Of Acute Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$294,163.00
Summary
In spinal cord injuries, the cord is compressed as a result of vertebral injury. Urgent relief of compression improves outcome, however, is difficult because of the complexity of pre-surgical management. Our data demonstrate that hypothermia stops compressive spinal cord injury, allowing decompression to be performed in a period that will benefit most patients. This project aims to undertake the studies necessary before beginning a human trial of hypothermia prior to decompressive surgery.
Investigations Of Cerebrospinal Fluid Flow In Extracanalicular Syringomyelia.
Funder
National Health and Medical Research Council
Funding Amount
$344,441.00
Summary
Cysts in the spinal cord (syringomyelia) develop in children and young adults with congenital spinal cord abnormalities such as spina bifida, and in people of all ages after spinal cord injury or meningitis. Syringomyelia causes pain and paralysis that usually does not improve even with treatment. The current lack of knowledge about the mechanism of spinal cord cyst formation and enlargement is preventing the development of effective therapy. We have previously shown that some types of spinal co ....Cysts in the spinal cord (syringomyelia) develop in children and young adults with congenital spinal cord abnormalities such as spina bifida, and in people of all ages after spinal cord injury or meningitis. Syringomyelia causes pain and paralysis that usually does not improve even with treatment. The current lack of knowledge about the mechanism of spinal cord cyst formation and enlargement is preventing the development of effective therapy. We have previously shown that some types of spinal cord cysts enlarge by the normal fluid surrounding the spinal cord being pumped around small arteries into the centre of the spinal cord. The mechanism of enlargement of post-traumatic spinal cord cysts remains unknown, and this debilitating type of syringomyelia remains difficult to treat. Our hypothesis is that post-traumatic spinal cord cysts also enlarge by fluid being pumped into them around small arteries. A further hypothesis is that reductions of arterial pulsations and of the pressure in the fluid surrounding the spinal cord will prevent or inhibit cyst enlargement. These hypotheses will be tested by examining fluid flow in models of post-traumatic syringomyelia in rats and sheep. We have established a model of post-traumatic syringomyelia in rats and the first phase of the project will be to refine and characterize this model and to reproduce it in sheep. The second phase will be to determine whether these cysts enlarge by a flow of fluid around small arteries that is driven by arterial pulsations, as they do in other types of syringomyelia. The final phase will be to determine whether reducing the pressure in the fluid around the spinal cord prevents cyst enlargement. Confirmation that these techniques prevent cyst enlargement would open up new possibilities for the treatment of human syringomyelia.Read moreRead less
Through the research supported by this Australia Fellowship, Prof Goulding will recruit and establish an internationally recognized team of researchers to study how nerve cells in the spinal cord function and contribute to the sensorimotor networks that control movement, posture, balance and protective reflexes. Sensory pathways in the spinal cord are important for protecting individuals from tissue damage and noxious insults and they also play an important role in regulating locomotion and move ....Through the research supported by this Australia Fellowship, Prof Goulding will recruit and establish an internationally recognized team of researchers to study how nerve cells in the spinal cord function and contribute to the sensorimotor networks that control movement, posture, balance and protective reflexes. Sensory pathways in the spinal cord are important for protecting individuals from tissue damage and noxious insults and they also play an important role in regulating locomotion and movement. They provide sensory feedback to the motor system to modulate it or activate particular reflexes. A multidisciplinary approach will be taken to dissect these circuits, using cutting edge mouse molecular genetics that allows specialized cell types to be studied and manipulated.Read moreRead less
The Molecular Basis For Target Selection In The Central Nervous System By Sensory Axons
Funder
National Health and Medical Research Council
Funding Amount
$251,325.00
Summary
The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct conne ....The normal function of the brain depends upon the specific connections that nerve cells make with each other. These connections are set up in the developing embryo when nerve cells send out long processes - axons - which grow towards their synaptic targets. How axons select their correct targets from amongst the millions of alternatives in the developing brain is unknown. A better understanding of this problem will help us develop therapies to assist regenerating axons re-establish correct connections following injury to the brain or spinal cord. We propose to use a simple model system, the embryo of the fruitfly Drosophila, to find molecules that are involved in this process of neuron target recognition - ' axon targeting' molecules - and to study how they work. Drosophila can be genetically manipulated in ways not possible in higher animals. Furthermore the simplicity of its nervous system means that we can determine the connections of individual nerve cells with a high degree of precision. In the first part of our project, we will examine Drosophila embryos that carry mutations in genes suspected to code for targeting molecules. We will stain individual sensory nerve cells in these embryos with dyes to reveal the anatomy of their axons in the brain. If sensory axons terminate abnormally in the brain of a given mutant, the affected gene is likely to code for an axon targeting molecule. In the second part of the study, we will investigate the functions of candidate axon targeting molecules using two approaches. Firstly, we will seek to determine whether the molecule acts in the sensory axons or in their target cells. Secondly, we will use time-lapse microscopy to study how the homing behaviour of the sensory axons is affected in mutant embryos. The results of these studies will lead us closer to an answer to the question: How do axons recognise their specific target cells in the brain?Read moreRead less
The Role Of Cell Adhesion Molecules In Regulation Of Axon Advance
Funder
National Health and Medical Research Council
Funding Amount
$426,006.00
Summary
All cells contain on their surface a class of molecules, cell adhesion molecules, that enable them to adhere to other cells in tissues. Cell adhesion molecules have long been known to be involved in the guidance of axons to their targets during development. However the molecular mechanisms by which these molecules act are largely unknown. We propose to use the powerful genetic tools available in the fruitfly to dissect the mechanisms by which two cell adhesion molecules promote axon growth.
Physiotherapist Led Stress Inoculation Intervention Integrated With Exercise For Acute Whiplash Injury
Funder
National Health and Medical Research Council
Funding Amount
$518,960.00
Summary
Physical and mental health outcomes following whiplash injury due to a road traffic crash are poor. Early stress system responses are associated with poor recovery. This study will investigate the effectiveness of a physiotherapist led stress inoculation intervention integrated with currently recommended exercise rehabilitation to improve health outcomes after whiplash injury.
Suppressor Of Cytokine Signalling-2 (SOCS2) And Its Role In Neuronal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$451,980.00
Summary
Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are ....Injury to the brain or spinal cord at present often results in permanent damage, such as paralysis, which is largely due to a failure of neurons to regrow at the injury site. In order to overcome this, we are trying to find ways of making new neurons grow, either from stem cells present in the nervous system or transplanted from cells grown in tissue culture. However, little is known about how a neural stem cell decides to become a neuron or another cell type, such as a glial cell and so we are examining factors which influence this process, which is called differentiation. Growth factors are important mediators of this process and suppressor of cytokine signalling (SOCS) proteins are important in determining how cells respond to growth factors. The overall aims of this project are to determine the role that SOCS genes and in particular, SOCS2 play in neural stem cell differentiation into neurons and glia, neuron process outgrowth and neuronal and glial injury responses in the nervous system. This will be examined in normal cells and cells which over-express or do not express SOCS2 genes. Understanding the biology of neural growth factor responsiveness may eventually allow us to devise therapeutic strategies for use following brain-spinal injury or disease, including generation of neurons from stem cells.Read moreRead less
Pre-clinical Evaluation Of Nano-membrane Dressings To Promote Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$188,600.00
Summary
This project will investigate whether a novel type of wound dressing can promote faster wound healing and reduce scarring. Time taken to heal is one of the best predictors of whether a wound will heal with significant scarring. The faster wounds heal the better. We have identified a new dressing with specific nano-scale pores that may promote faster healing. This dressing will be tested in the best model of human wound healing with the potential to progress to clinical trials if successful.