Improving Muscle Function After Injury: Novel Tissue Engineering Strategies For Exercise, Surgery And Sports Medicine
Funder
National Health and Medical Research Council
Funding Amount
$288,210.00
Summary
Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel thera ....Muscles can be injured by excessive strains when playing sports, in road and workplace accidents, and during plastic and reconstructive surgery. Some surgeries require an unavoidable interruption to the muscle's normal blood supply (called 'ischaemia'). Subsequent return of the muscle's blood supply (reperfusion) is problematic in that a severe secondary muscle injury can ensue mediated by the influx of damaging free radicals when blood flow is restored. Tissue-engineering provides a novel therapeutic approach to restore muscle structure and function to damaged muscles after injury or disease. Our recent research using controlled release of growth factors from biodegradable hydrogels has exciting application for muscle repairafter injury. We will utilize these cutting edge tissue engineering strategies to deliver to damaged muscles a hydrogel containing controlled delivery (slow release) microcapsules loaded with an anabolic agent (the beta-agonist, formoterol) and-or a growth factor (IL-15) designed to enhance functional muscle repair after three distinct but clinically relevant models of muscle injury: a) crush injury: A model for muscle injuries on the sports field, in the workplace, and those associated with road trauma; b) ischaemia-reperfusion injury: a model for muscle damage associated with surgical interventions, muscle transfers for functional restoration, and other injuries associated with plastic and reconstructive surgery; and c) contraction-induced injury: a model for strain injuries such as hamstring muscle tears that can occur on the sports field. After injury we will assess functional muscle repair using a comprehensive series of histological, biochemical, molecular, immunochistochemical, and physiological techniques. The research has broad application to exercise and clinical medicine; including sports, emergency and rehabilitation medicine, and plastic, reconstructive, and orthopaedic surgery.Read moreRead less
A Prospective Study Of Concussion In Children And Adolescents: Diagnosis, Recovery And Risk Factors For Poor Outcome.
Funder
National Health and Medical Research Council
Funding Amount
$277,000.00
Summary
Concussion is one of the most common neurological injuries and represents a significant public health issue in Australia. The most common consequences of concussive injuries are reduced attention, slowed response speeds and memory impairment. These cognitive processes are critical for performing common day-to-day activities in childhood and adolescence (e.g. acquiring new knowledge and skills, attending to school work). Approximately 20% of concussive injuries occur during participation in organ ....Concussion is one of the most common neurological injuries and represents a significant public health issue in Australia. The most common consequences of concussive injuries are reduced attention, slowed response speeds and memory impairment. These cognitive processes are critical for performing common day-to-day activities in childhood and adolescence (e.g. acquiring new knowledge and skills, attending to school work). Approximately 20% of concussive injuries occur during participation in organised sport. In adult populations, there are now evidence-based guidelines for the diagnosis and management of concussion in sport. Few well-controlled studies exist to identify the frequency and outcome of such injuries in child and adolescent populations, and there are currently no guidelines for diagnosis and management of concussion in children. Further, the academic and social consequence of concussion for the child remains unknown. This study will investigate the cognitive and behavioural outcomes of concussion in young children and adolescents and will use this information to modify and validate currently available adult concussion diagnosis and management paradigms for application with this population. This study will also investigate risk factors for poor outcome following concussion in children and adolescents, and provide age-appropriate data for use in the medical, behavioural and educational management of concussed children and adolescents. A total of 3000 children aged between 10 and 18 years will be recruited to participate in this study. All participants will undergo a baseline evaluation consisting of memory and attention tests, a behavioural rating scale, and measures of educational ability. Participants parents will also provide general health and demographic information. Children who are concussed during the year will be re-assessed within 48 hours of injury and again at 5 days, 10 days and 30 days post-injury to track recovery.Read moreRead less
Adaptation Of Muscle To Eccentric Exercise And Its Clinical Applications 194272
Funder
National Health and Medical Research Council
Funding Amount
$196,410.00
Summary
Work in this laboratory has concentrated on Delayed Onset Muscle Soreness (DOMS), the soreness felt for several days after unaccustomed exercise. This is particularly so when the exercise involves stretching of active muscle, called eccentric exercise, at longer muscle lengths. DOMS is due to microscopic muscle damage. A rapid training effect, leading to reduced soreness from a subsequent bout of similar exercise, has been identified by us as due to a specific structural adaptation. This results ....Work in this laboratory has concentrated on Delayed Onset Muscle Soreness (DOMS), the soreness felt for several days after unaccustomed exercise. This is particularly so when the exercise involves stretching of active muscle, called eccentric exercise, at longer muscle lengths. DOMS is due to microscopic muscle damage. A rapid training effect, leading to reduced soreness from a subsequent bout of similar exercise, has been identified by us as due to a specific structural adaptation. This results in the optimum length for tension generation moving to longer muscle length so that the muscle is less likely to be damaged during subsequent stretches. Hypothesizing that gross muscle tears arise from the microscopic damage, we have begun investigating whether eccentric exercise training can prevent hamstring muscle injuries. We have shown that eccentric exercise shifts the optimum length for contraction in human hamstring muscles. We are now examining athletes with past injuries, known to be likely to re-injure. Other experiments are designed to show that sports that cause injury do indeed include eccentric exercise of the hamstring muscles. We are also investigating the effectiveness of eccentric exercise in treating apparently normal children who compulsively walk on their toes. We have built monitoring equipment and are monitoring both conventional and exercise based treatments designed to shift muscle optimum length to longer lengths to allow the children to place their heels on the ground. Finally, most muscles contain different fibre types, distinguished mainly by their speed of contraction. It has been suggested that they are not all uniformly susceptible to damage from eccentric exercise, a result not predicted by our theory. However, we hypothesize that secondary factors, particularly the length for generating optimum tension, may be responsible for these differences. We plan to test this idea by measuring properties of different types of motor units.Read moreRead less
Changes In Motor Control And Kinaesthetic Sensations After Eccentric Exercise.
Funder
National Health and Medical Research Council
Funding Amount
$287,250.00
Summary
It is a well-known observation that after a period of intense exercise we are unsteady on our feet and are clumsy when attempting to make precision movements. Such impressions are particularly marked after eccentric exercise, during which the contracting muscles are forcibly lengthened. Activities such as walking downhill, skiing and horse riding involve eccentric exercise. The debilitating consequences of this kind of exercise are attributed, not just to the post-exercise effects of fatigue, bu ....It is a well-known observation that after a period of intense exercise we are unsteady on our feet and are clumsy when attempting to make precision movements. Such impressions are particularly marked after eccentric exercise, during which the contracting muscles are forcibly lengthened. Activities such as walking downhill, skiing and horse riding involve eccentric exercise. The debilitating consequences of this kind of exercise are attributed, not just to the post-exercise effects of fatigue, but to loss of muscle force from damage to fibres. Eccentric exercise also leads to longer term effects. The breakdown of the damaged tissue leads to sensations of stiffness and soreness the next day. This application proposes experiments aimed at studying a number of effects of eccentric exercise on motor control, and establishing the muscle, spinal and brain levels at which they occur. Three studies are planned. In the first, the question will be explored whether we are less able to use the motor areas of our brains to execute voluntary contractions after exercise. So fatigue is not just a matter of exhausted muscles but perhaps also exhausted brains. We will use brain and spinal cord stimulation to explore this point. Then we plan to listen to single motor units, the basic elements of muscle control, to try to understand the mechanism by which the brain minimises the debilitating effects of fatigue. Finally we want to examine subjects' ability to locate their limbs in space as a means of providing a basis for the clumsiness we experience after intense exercise. These are all important issues relevant to clinical medicine and rehabilitation as well as sports science and exercise.Read moreRead less
ANALYSIS OF KNEE KINEMATICS- An MRI Study Of The Normal, Anterior Cruciate Injured, And Reconstructed Knee.
Funder
National Health and Medical Research Council
Funding Amount
$161,320.00
Summary
People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one norma ....People with anterior cruciate ligament damage to the knee tend to develop osteoarthritis in this knee, perhaps because the instability produced by the ligament tear changes the patterns of wear on the joint surfaces. There are several studies using cadaver knees which examine the impact on the joint surfaces of cutting the anterior cruciate ligament, but very little of people moving voluntarily. This study plans to use MRI images of people with a torn cruciate ligament in one knee, and one normal knee. The subjects will simulate a squat inside the MRI magnet against a weighted footplate. The images will be taken at fifteen degree intervals of knee movement. The contact points between the joint surfaces will be measured and compared to the normal knee. This imaging will be repeated after surgical repair, and then again two years later, to assess whether the normal movement pattern has been restored.Read moreRead less
Risk Factors For Serious Farm-work Related Injury Among Adult Males
Funder
National Health and Medical Research Council
Funding Amount
$665,930.00
Summary
This study addresses occupational injury among male adult farm workers. The health and safety performance of agricultural industries is among the worst in Australia. A recently published study of work-related fatalities from 1989 to 1992 found that rural industries ranked third, with a fatality rate 3-4 times that for all industries. The rural industries accounted for 80 deaths annually. Best estimates place the cost of farm injury between $0.5 and $1.29 billion per year. This study is designed ....This study addresses occupational injury among male adult farm workers. The health and safety performance of agricultural industries is among the worst in Australia. A recently published study of work-related fatalities from 1989 to 1992 found that rural industries ranked third, with a fatality rate 3-4 times that for all industries. The rural industries accounted for 80 deaths annually. Best estimates place the cost of farm injury between $0.5 and $1.29 billion per year. This study is designed to contribute to farm injury prevention by: (1) identifying factors associated with a higher risk of serious injury among adult farm workers and (2) determining the proportions of the farm workforce who are exposed to various injury risks. The study will recruit 300 seriously injured or killed farm workers from regional Victoria and collect information about themselves, their working life and the property on which they work. This information will be compared with 600 randomly selected farm workers who are not seriously injured to determine which personal, work and environmental factors place farm workers at higher risk of injury. The study will lead to the development of new or more refined prevention strategies and programs. A study of this kind has not been conducted before in Australia and would contribute to a continuing scientific basis for selection of interventions for farm injury and targeting of prevention programs, at a time of increasing momentum in agricultural health and safety.Read moreRead less
The Neural Reaction To Injury: Clues To The Cause And Prevention Of Acquired Brain Damage And Alzheimer's Disease.
Funder
National Health and Medical Research Council
Funding Amount
$390,326.00
Summary
The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the compl ....The cellular mechanism underlying neuronal degeneration following head trauma and Alzheimer?s disease is not known and represents the major impediment to developing therapeutic strategies to protect nerve cells. This grant application will utilise a variety of modern research methods to determine the key changes in the brain that are associated with the response of nerve cells to physical trauma. These include not only the structural alterations that immediately follow such injury, but the complex cellular and gene expression changes that determine the ultimate fate of the cell. Both acquired brain injury and degenerative conditions such as Alzheimer?s disease represent an enormous health, social and economic burden. Furthermore, with predictions that Alzheimer?s disease will increase by 3-4 times by the middle of the next century due to the Oaging? of the population, it is becoming even more crucial to establish effective therapeutic interventions. The animal models investigated in this project can be used to unravel the crucial neuronal alterations associated with head trauma and the early stages of Alzheimer?s disease and, more importantly, may be the key to discovering novel strategies to prevent neuronal degeneration in these conditions.Read moreRead less
Characterisation Of Substance P Antagonists As A Novel Therapeutic Intervention For Use In Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$241,650.00
Summary
Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of ....Traumatic brain injury (TBI) is responsible for more deaths in Australians under 45 years of age than any other cause. The economic and social cost of head injury to the community is enormous with billions of dollars spent each year on the management and rehabilitation of trauma patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have demonstrated that much of the morbidity following TBI is associated with the development of a secondary injury process that occurs between hours to days after the insult. This delayed progression of injury suggests that appropriate pharmacologic intervention can prevent, or at least attenuate, this secondary injury process with a resultant improvement in outcome. Over the past 15 years, a number of groups, including ours, have been investigating the secondary mechanisms associated with the development of functional deficits after TBI. Our previous studies have demonstrated that decline in brain free magnesium is associated with functional deficits after experimental brain injury, and that magnesium administration after injury can improve outcome. Magnesium is now on clinical trial as a pharmacologic intervention. Recent studies have suggested that magnesium decline facilitates neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death. Although a number of neuropeptides have been implicated in this process, it is thought that substance P release is closely associated with these pathophysiological processes. Therefore, inhibiting neuropeptide release, or inhibiting substance P binding, may offer a novel therapeutic approach for the attenuation of oedema and development of neurologic deficits after TBI. This proposal will use a combined biochemical, pharmacologic and behavioural approach to characterise the role of neuropeptides in brain trauma, and attempt to develop a novel therapy for use in clinical trauma.Read moreRead less