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
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.
Immediate Cooling And Emergency Decompression (ICED) For The Treatment Of Spinal Cord Injury: Pilot, Safety And Feasibility Studies
Funder
National Health and Medical Research Council
Funding Amount
$600,008.00
Summary
Victims of Spinal Cord Injury are young, have severe paralysis, complex needs and high lifetime costs. Although urgent surgery greatly improves outcome, it is difficult to achieve because of logistical difficulties. To expand the time window for early surgery, it is proposed to immediately cool patients. This project will conduct the pilot studies necessary before commencing a clinical trial of immediate cooling and emergency decompression (ICED) in patients with cervical spinal cord injuries.
Therapeutic Development Of A Novel EphA4 Antagonist For Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$687,105.00
Summary
Spinal cord injuries impose a significant burden on patients and their carers. At present, there are no treatments for spinal cord injury that provide functional improvement. This research program will develop a novel therapeutic molecule, EphA4-Fc, which promotes axonal regeneration and delivers significant functional improvement. We will determine the most effective protocol for EphA4-Fc administration and the physiological and functional outcomes of these treatment regimes.
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.
Translation Of Abdominal Functional Electrical Stimulation From A Research Tool To Clinical Practice
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
People with a spinal cord injury to the neck are often unable to move their arms and legs, a condition known as tetraplegia. Tetraplegics are also unable to use their abdominal muscles, reducing breathing and bowel function. This project will use electrical pulses to make their abdominal muscles contract, improving breathing and bowel function. The results will be used to develop a program that can be used in all hospitals, reducing illness in tetraplegia and saving the health service money.
Effectiveness Of Ghrelin Receptor Agonists To Limit The Extent Of Tissue Damage Caused By Traumatic Injury To The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$592,002.00
Summary
Ghrelin is a naturally occurring compound that under adverse conditions can activate specific receptors on cells around the body to enhance their survival. These receptors are also present in the spinal cord, but ghrelin doesn't enter the spinal cord. We will investigate a new group of compounds that can enter the spinal cord and activate these receptors to see if this can reduce the amount of damage that occurs after a spinal cord injury. Less tissue damage would mean less permanent disability.