Neuroprotection Against Parkinson’s Disease With Remote Photobiomodulation
Funder
National Health and Medical Research Council
Funding Amount
$314,818.00
Summary
Treating the head of rodents with low-intensity 670nm light protects against Parkinson’s disease (PD), but the large size of the human skull and brain precludes clinical translation of this treatment. We have discovered that the brain is also protected when light is targeted at peripheral tissues (e.g. a limb), overcoming problems of delivery. This project aims to optimise this treatment and better understand how it works, to lay the scientific basis for a clinical trial.
Elucidating The Neuroprotective Region Of The Amyloid Precursor Protein (APP) Following Traumatic Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$467,556.00
Summary
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and to date there is no therapy to ameliorate this injury. There is increased production of the amyloid precursor protein (APP) following TBI and recent studies have found that APP possesses neuroprotective traits. It is the aim of the current studies to delineate the specific active neuroprotective region of APP and develop them as novel therapeutic interventions for use in TBI.
Assessing The Efficacy Of Safe And Simple Neuroprotective Treatments For Chronic Degenerative Conditions Of The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Current treatments for age-related diseases of the central nervous system (CNS) are limited. We have shown in animal models of acute CNS degenerations that treatment with saffron or low energy infrared light is strongly protective. This project will determine if these treatments prevent CNS damage and dysfunction in animal models of chronic degenerations and add to knowledge of how these treatments work. This research should lay the foundation for testing these novel treatments in humans.
Effectiveness Of Ghrelin Receptor Agonists To Limit The Extent Of Tissue Damage Caused By Traumatic Injury To The Central Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$592,002.00
Summary
Ghrelin is a naturally occurring compound that under adverse conditions can activate specific receptors on cells around the body to enhance their survival. These receptors are also present in the spinal cord, but ghrelin doesn't enter the spinal cord. We will investigate a new group of compounds that can enter the spinal cord and activate these receptors to see if this can reduce the amount of damage that occurs after a spinal cord injury. Less tissue damage would mean less permanent disability.
Substance P Antagonists As A Novel Therapeutic Intervention In Stroke
Funder
National Health and Medical Research Council
Funding Amount
$318,267.00
Summary
Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and ....Stroke is the major cause of disability in adults over 45 years of age in Australia. The economic and social cost of stroke is enormous with billions of dollars spent each year on the management and rehabilitation of stroke patients. Despite the enormity of this public health problem, no effective treatment currently exists. A number of studies have now demonstrated that much of the morbidity following stroke is associated with the breakdown of the blood brain barrier, development of oedema, and subsequent brain damage in areas surrounding the central region of the stroke. These events develop over hours to days following the stroke and are known as secondary injury. 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. Nonetheless, few interventions are available that can limit this development. Our own recent studies have demonstrated that regions in brains which demonstrate the presence of stroke also exhibit signs of neurogenic inflammation, which has been associated with oedema formation, oxidative damage and cell death in other tissues. 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. Thus, inhibiting substance P binding may offer a novel therapeutic approach to attenuating oedema formation and the development of neurologic deficits following stroke. This proposal will utilise a combined biochemical, pharmacologic and behavioural approach to characterize the role of neurogenic inflammation in the development of oedema and neurologic deficits following stroke. Moreover, we will develop a novel pharmacotherapy that can potentially be used in the treatment of clinical stroke.Read moreRead less
Cell Death In The Retina: Analysing The Switch That Triggers Dependency On Target-derived Trophic Factors
Funder
National Health and Medical Research Council
Funding Amount
$428,414.00
Summary
Construction of the developing nervous system in the embryo involves the creation of nerve cells and their connections, but also involves loss of a proportion of these cells prior to maturation. We will study this process of cell death and how developing nerve cells switch on their dependency to survival factors. In so doing we will better understand what happens when brain development goes wrong and also devise new ways to protect nerve cells in the injured or degenerate adult nervous system.
Evaluation Of Combined Mild Hypothermia And Magnesium As A Neuroprotective Therapy Following Cerebral Ischaemia/stroke
Funder
National Health and Medical Research Council
Funding Amount
$310,286.00
Summary
Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.Read moreRead less
Compromised Fetal Brain Development: Neurogenesis And The Potential For Therapeutic Intervention.
Funder
National Health and Medical Research Council
Funding Amount
$497,280.00
Summary
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and ....Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy) that there is a reduction in neurons and in the connections between them. This may result from a reduction in number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1) determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis, apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.Read moreRead less