INVESTIGATIONS ON THE REGULATION OF INTERVERTEBRAL DISC CELL MATRIX METALLOPROTEINASES
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem w ....Degeneration of the intervertebral disc is a painful disabling condition with major socioeconomic consequences. Medical problems associated with disc degeneration and back-pain, of sufficient severity to warrant consultation with a physician, are experienced by 90% of the population some time during their lives. In man, back pain increases in incidence in the third and fourth decades of life, peaks in the fifties and declines thereafter. Changes in population demographics indicate this problem will increase in severity over the next few decades. American Bureau of Census data indicate that between 1990 to 2010 the number of people >45 years will increase from 82 to 124 million, the number of elderly in emerging countries will also increase between 200 to 400% in the next 30 years. In the United States, back-pain is the second most common reason that people visit a physician and medical conditions related to back-pain account for more hospitalisations than any other musculoskeletal disorder. Despite its high incidence, associated problems of incapacity and economic implications, costed at $100 million per annum in Australia in 1992, and US$100 billion globally in 1999-2000 (Dorland Data Networks, PA, USA) the causes of low back-pain are still poorly understood. Disc disease is responsible for 23-40% of all cases of low back-pain. The management of discogenic low back-pain is currently empirical, directed either toward life-style changes to minimise symptomatology or to surgical resection or spinal arthrodesis to restrict articulation. Based on our recent findings and those of colleagues over the last 16 years, it is our strong conviction that it should be possible with a better understanding of disease mechanisms and with the use of modern technologies to inhibit, reverse or ideally prevent disc degeneration. Without such basic research there will be no scientific foundation upon which prospective therapies may be based.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
Connectivity Of Regenerating Axons Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
Our objective is to thoroughly investigate the connections made by regenerating nerve fibres in mice which are treated with specific compounds to inhibit scarring as well as with active exercise following spinal cord injury. This will provide evidence of the potential of these compounds as a therapeutic intervention. Understanding how the nervous system rewires following exercise intervention will provide insights as to how new connections can be shaped to ensure optimal recovery of function.
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
Differentiation Of Respiratory Behaviour In The Mammalian Fetus
Funder
National Health and Medical Research Council
Funding Amount
$434,839.00
Summary
Mammalian fetuses are highly active from early in gestation, manifesting patterns of activity that are gradually transformed throughout fetal life, ultimately producing a repertoire of behaviours essential for postnatal survival. These behaviours are of fundamental importance to animals, and none more so than breathing which must perform effectively from the moment of birth. We plan to examine neural control mechanisms that transform a primitive pattern of breathing in the early gestation fetus ....Mammalian fetuses are highly active from early in gestation, manifesting patterns of activity that are gradually transformed throughout fetal life, ultimately producing a repertoire of behaviours essential for postnatal survival. These behaviours are of fundamental importance to animals, and none more so than breathing which must perform effectively from the moment of birth. We plan to examine neural control mechanisms that transform a primitive pattern of breathing in the early gestation fetus into the functional form that effectively ventilates the lungs after birth. In addition to examining the prenatal development of breathing, our program will focus on the developmental fate of a transient behaviour restricted to early development. This early behaviour plays a fundamental role in the development of the motor system before being extinguished under the influence of supraspinal inputs. This program will therefore provide a basis for understanding the mechanisms by which the brain establishes control of the motor circuits of the spinal cord during development. Further, the program is designed to provide a basis for understanding the respiratory problems so common in the preterm human infant.Read moreRead less
Neural Circuits Producing Pelvic Vasodilation In Females
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions ....The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions of these nerves. An important part of this neural pathway is a group of nerve cells in the spinal cord that connects the central nervous system with peripheral nerves in the reproductive organs - these are called preganglionic neurons. Recently we discovered that a major pathway from the spinal cord to the pelvic blood vessels in females leaves the spinal cord at a different level (lumbar) from that thought previously (sacral level). Currently there is no information on how these lumbar preganglionic nerves in females are connected to other nerve pathways that are active during sexual activity, and how they integrate signals from both the internal organs and the brain. We will use an array of modern cellular techniques together with direct observation of dilation in isolated uterine arteries to discover how these nerve cells are wired up in circuits in the spinal cord. This information is vital for us to understand the factors producing increased blood flow in normal sexual activity, and how these might be altered in inflammation or in conditions where there could be selective damage to one nerve pathway and not the other, such as after pelvic surgery, spinal cord damage at different levels, or stimulation of the spinal cord for treatment of chronic pain. Our study also will help understand referred pain and sensations of discomfort in abdominal and pelvic organs.Read moreRead less
Thalamic Neuroplasticity And Pain Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$299,520.00
Summary
Pain is a major problem for people with spinal cord injuries and is common, severe and difficult to treat. There is increasing evidence to suggest that pain may be linked to specific changes in some brain regions following a spinal cord injury. Several possible brain changes have been suggested but not investigated fully and have different implications for treatment. This project aims to characterise these brain changes with the purpose of developing novel effective and targeted treatments.
Chronic neck pain is difficult to treat and can result in a complex set of symptoms, including dizziness, disturbed vision, and exaggerated pain responses in the upper torso and arms. Thus, there is a need to develop new treatments for this debilitating condition. This project will study how damage to structures in the neck alters the excitability of nerve cells in the upper cervical spinal cord. The results will provide a foundation for development of therapies to treat chronic neck pain.