Repairing The Injured Spinal Cord: Potential For Human Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult ....Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult rats can lead to limited functional recovery of hindlimb movement. We used peripheral ensheathing cells because, in humans, such cells can be obtained relatively easily and they reduce problems of tissue rejection. We found that peripheral cells are as effective as previous reports using central ensheathing cells. Our overall aim now is to advance towards the use of olfactory cells in human spinal cord injury, by trialing 3 procedures of clinical relevance: a) to test whether human olfactory cells can also support functional recovery in rats. Human cells can be obtained from the nose by a simple biopsy procedure. If they able to support regeneration, this will open the way for their use in autografts in human paraplegia. b) to delay the time when the olfactory cells are applied to the injured cord. At present, neurosurgeons are not be willing to treat the cord immediately after the injury, because of the risk of causing further damage. This trial is designed to test whether delayed treatment is still effective. c) to test the effectiveness of the cells after bruising, rather than cutting, the cord. Bruising is a more common type of injury in people, hence it is necessary to know how these cells respond to this type of damage. These procedures have been chosen to move our basic research closer to clinical application. Although treatment in humans is still a long way off, these basic studies are essential if conditions like paraplegia are eventually to become treatable.Read moreRead less
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
Orthostatic Tolerance During FES-evoked Stepping In Paraplegia: A Safety And Viability Study
Funder
National Health and Medical Research Council
Funding Amount
$244,900.00
Summary
In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES ....In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES present the SCI person with a means of restoring upright mobility and reinstating functional tasks. Yet, while this technological innovation remains promising for optimising functional outcomes after SCI, there remains a distinct lack of knowledge of the physiological stresses placed upon the individual. In this preliminary safety and viability study, the physiological implications central to enhanced upright mobility will be investigated during FES-evoked prolonged stepping. The responses during FES-stepping will be contrasted with the responses observed during stepping performed without FES. The study will investigate the blood pressure responses during FES-gait, but also address possible physiological mechanisms underlying those blood pressure responses. The findings from this study will identify whether there is a phsiological limitation to the performance of FES-evoked functional mobility. Current physiotherapy practice recognises blood pressure control and orthostatic hypotension as a significant barrier to functional standing and stepping, yet little is known about the physiology underpinning the condition. If FES does present a limitation to the performance of upright functional activities, this study will also assist in devising alternative physiotherapy gait training regimens.Read moreRead less
Investigation Into The Roles Of A Novel Vertebrate Gene, S52, In CNS Development And Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$272,389.00
Summary
Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development an ....Developmentally regulated genes when mutated or deleted can cause a variety of diseases including neurological diseases in humans. It is therefore important to understand the fundamental molecular genetics of development. We have discovered a novel human gene, termed S52, and its equivalent gene in the mouse. The predicted protein derived from these genes would indicate that S52 protein may interact with other proteins, possibly nerve growth factors, in the body to regulate normal development and possibly facilitate the survival of nerve cells in embryos. Strikingly, the worm C. elegans, an evoluationary very distant animal, also has a very similar gene to human. The fact that the protein has been so conserved throughout evolution supports the idea that S52 function is important in development. S52 mRNA is expressed in the developing brain, particularly in a special group of cells called the floor plate. Floor plate is a tissue that has ability to organize the patterning and differentiation of cells within the developing brain. S52 is also expressed in motor neurons in early stages of development and later in a subset of dorsal spinal cord neurons. We have mapped S52 to the short arm of human chromosome 2 (2p15-22). This region of chromosome 2 is linked to several human genetic diseases with neurological defects. Based on our preliminary data, we think S52 is not only important for normal brain development but may be mutated in a human neurological disease called Spastic Paraplegia Type 4 (SPG4) which is characterized by a degeneration of nerve cells in the spinal cord. The aim of this project is to further our understanding of the function of this gene and investigate its role in disease. This knowledge will contribute to an overall increase in our understanding of the molecular basis of brain development and neurological disease in humans.Read moreRead less
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less