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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
Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin ....Current treatments for chronic pain are limited in their success. This emphasises the need for new insights into the basic mechanisms and nervous system circuitry underlying altered or chronic pain states. Work in animals and patients with chronic pain shows that certain brainstem centres communicate, via descending spinal cord pathways, with small nerve cells in the superficial dorsal horn (SDH) of the spinal cord. These SDH neurones receive and process pain-signalling information from the skin and internal organs, and receive inputs from descending pathways. This descending input can either inhibit or enhance the activity of SDH neurones and subsequent pain perception. Till now it has been difficult to directly examine how descending pain pathways influence the small SDH neurones in the spinal cord. A new approach, which has been developed in our laboratory, now allows us to record from these very small SDH neurones in the spinal cord of an intact deeply anaesthetized mouse. In addition, our technique allows us to examine the recorded SDH neurone s responses to functionally relevant stimuli (brushing or pinching the hindpaw) as well as its physiology and anatomy. This project will use our new techniques to examine the effects of activating descending brainstem pathways that alter the way painful stimuli are processed in the spinal cord. The effects of altered levels of inhibition in the spinal cord will also be studied by using mice with naturally occurring mutations in their inhibitory glycine receptors. We believe a more complete understanding of pain processing mechanisms will be achieved by examining the role of descending pathways in an intact animal preparation. Such data are essential for the development of drug therapies that can successfully target pain syndromes.Read moreRead less
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.
Reduction Of The Cardiovascular Response Of Psychological Stress Through Blockade Of Orexin’s Action On One Of Its Receptors.
Funder
National Health and Medical Research Council
Funding Amount
$394,925.00
Summary
Anxiety, fear of challenges, frustration are part of modern life stressors. Our body reacts to these stressors by increasing blood pressure and heart rate, which in turn can harm our cardiovascular system and precipitate cardiovascular accidents. In this project we test a new class of drugs that act on a neurochemical system implicated in these particular responses. If our hypothesis is correct, one of these drugs could be used to relax the cardiovascular system and protect it in times of stress ....Anxiety, fear of challenges, frustration are part of modern life stressors. Our body reacts to these stressors by increasing blood pressure and heart rate, which in turn can harm our cardiovascular system and precipitate cardiovascular accidents. In this project we test a new class of drugs that act on a neurochemical system implicated in these particular responses. If our hypothesis is correct, one of these drugs could be used to relax the cardiovascular system and protect it in times of stress.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
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.