VicCPchild- Prospective Cohort Study Of Children With Cerebral Palsy
Funder
National Health and Medical Research Council
Funding Amount
$613,587.00
Summary
Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocati ....Cerebral palsy is the most common cause of physical disability in children affecting 1 in 500 young Australians. While the brain lesion is static, the musculoskeletal problems are progressive and require lifelong management (cost of US$946,000 over life per person). Only large prospective population-based studies give a true indication of the incidence of physical problems, determine the pathway(s) to outcome and determine the best pathways to successful treatment and efficient resource allocation. The broad aim of this project is: This population based cohort study (n - 240) aims to determine the pathway to motor outcome from diagnosis at 18 months to 5 years based on the nature of the brain injury at 24 months (structural MRI of the nature, location and timing of the brain lesion). Secondary Aims: Determine the rate of musculoskeletal deformity (hip displacement, spasticity, muscle contracture). Potential impact of medical co-morbidities (nutrition, epilepsy, respiratory problems) Patterns of participation and HRQOL. Patterns of medical resource use: treatment costs and outcomes. This study will: Allow clinicians to better the likely functional outcomes of children with CP from an earlier age based on the rate and limit of gross motor development and nature and severity of the brain lesion, determine the nature and timing of physical deformities to aid prevention and treatment; provide information on resource use for future planning and organisation of medical and therapy services. This in turn will give more accurate prognostic counseling as well as target areas for early therapy. Our multidisciplinary research group is uniquely placed to conduct this world-first study with access to two entire birth years of children linked to our Victorian Cerebral Palsy Register. Recruitment is conducted at both the Royal Children's Hospital and the Monash Medical centre in order to ensure state wide referral and easy access for families.Read moreRead less
The Neurophysiology Of Abnormal Motor Development In Preterm Children
Funder
National Health and Medical Research Council
Funding Amount
$479,967.00
Summary
Better neonatal care has improved survival of prematurely born children. While most of these children will have no obvious brain lesion and attend mainstream schools, many will experience motor and cognitive difficulties and problems with social adjustment. However, the physiological mechanisms underlying this dysfunction are unknown. We will study preterm and term born children to elucidate the physiological mechanisms underlying motor and cognitive dysfunction associated with prematurity.
Cell Type Specification In Developing CNS: Functional Analysis Of Sox14
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are ....The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are maintained in the adult. This has been largely due to a lack of efficient and reliable methods to identify and study interneurons. We have previously discovered that a gene termed Sox14 is active in distinct interneuron groups in the embryonic brain and spinal cord. Sox14 is a member of the Sox gene family, many of which act as genetic switches to control cell and tissue development. We found that Sox14 has been extremely well conserved throughout evolution and is active in similar interneuron groups in a number of animal species. These studies led us to hypothesise that Sox14 controls a critical molecular step in the generation of certain interneurons that may be involved in reflexes, locomotion or motor coordination. In this project, we will investigate both the role of Sox14 in interneuron development and the functions of interneurons in which this gene is active. We will do so by combining modern molecular and genetic techniques with physiological approaches. This project will reveal critical molecular steps in CNS development and determine the functions of a specific group of interneurons. To this end, we will generate mouse strains in which a specific group of interneurons are genetically marked and can be manipulated during development. We envisage that these mice with 'modified brain circuits' will become unique resources for future investigations of selected interneuron types and their functions.Read moreRead less
Neural Mechanisms Associated With Recovery Of Function Following Motor Cortical Lesions
Funder
National Health and Medical Research Council
Funding Amount
$196,415.00
Summary
Damage to movement control areas in the brain early in life (e.g. cerebral palsy) or in adulthood (e.g. stroke, tumours) results in motor weakness and loss of skill; over a period of many months there is gradual recovery of function. The neural mechanisms that are associated with functional reorganization of the brain and motor recovery are not well understood. This project plans to use animal experiments to identify the location of regions in the brain that undergo neural reorganization and com ....Damage to movement control areas in the brain early in life (e.g. cerebral palsy) or in adulthood (e.g. stroke, tumours) results in motor weakness and loss of skill; over a period of many months there is gradual recovery of function. The neural mechanisms that are associated with functional reorganization of the brain and motor recovery are not well understood. This project plans to use animal experiments to identify the location of regions in the brain that undergo neural reorganization and compensate for lost function. Following brain lesions detailed mapping of the motor areas of the brain and a careful study of movement disabilities will be performed. The study will attempt to identify changes in motor maps that indicate neural reorganization and relate these changes to motor recovery. The results of this study will be used in future projects to test training programs, drugs and neural prosthesis on neural reorganization and recovery of function. Eventually the information may be used to direct pharmacological and physiotherapeutic interventions, and motor rehabilitation programs for optimal recovery of function.Read moreRead less
Evaluation Of Orally Active Anti-inflammatory C5a Receptor Antagonists In A Transgenic Rat Motor Neurone Disease Model
Funder
National Health and Medical Research Council
Funding Amount
$533,578.00
Summary
Motor neurone disease is a rapidly progressive and incurable disease, usually ending in death within 3-5 years of diagnosis. The disease usually arrives without warning, and results in a progressive loss of muscle control. There is no effective treatment, and available drugs increase life span by a few weeks at best. There is evidence that the disease involves an inflammatory component, but available anti-inflammatory drugs are ineffective. We have developed a new class of anti-inflammatory drug ....Motor neurone disease is a rapidly progressive and incurable disease, usually ending in death within 3-5 years of diagnosis. The disease usually arrives without warning, and results in a progressive loss of muscle control. There is no effective treatment, and available drugs increase life span by a few weeks at best. There is evidence that the disease involves an inflammatory component, but available anti-inflammatory drugs are ineffective. We have developed a new class of anti-inflammatory drugs, known as C5a antagonists, and in preliminary experiments have shown they are therapeutically effective in a transgenic rat model of motor neurone disease. We propose to investigate in more detail how these drugs work in the rat model, and demonstrate that a specific inflammatory pathway, which we can now block, is responsible for some of the disease's progression. This work may lead to an entirely new class of drugs being used to treat patients with this drastic disease.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
The Efficacy Of Novel, Non-robotic Devices To Train Reaching Post Stroke
Funder
National Health and Medical Research Council
Funding Amount
$491,605.00
Summary
Up to 50% of stroke survivors are left with upper limb disability that limits their daily activities and their paralysis is so severe that it excludes them from training with the most effective methods. This study is a clinical trial of innovative new techniques to assist people with severe upper limb paralysis to reach following stroke. Positive results are likely to reduce disability in a large number of stroke survivors and has the potential to be used by other patients with paralysis.