Long Term Outcome From Early Childhood Brain Injury: 10 Year Follow Up
Funder
National Health and Medical Research Council
Funding Amount
$338,900.00
Summary
The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally he ....The primary aim of this project is to further improve our understanding of the long-term consequences of childhood traumatic brain injury (TBI). Over the past decade our research team has ascertained a sample of children sustaining TBI, and systematically followed their progress over a 5-year period. The project has an international reputation, and is unique in terms of length of follow-up, prospective design and representative, well-maintained sample. Our findings challenge the traditionally held view that children are resilient and recover fully from early brain insult. Rather, we have shown that, up to 5 years post-TBI, many children experience impairments in physical, cognitive and behavioural function. These impairments result in educational, vocational, social and emotional problems, limiting the child's capacity to meet developmental expectations and achieve adequate quality of life. The implication is that these problems will lead to life-long disability, resulting in high levels of individual, family and community burden. However, with follow-up data limited to 5 years, there remains a possibility that ongoing developmental processes may support an extended recovery period in childhood TBI, in comparison to the 2-year period cited in adult models. The review of this sample, 10 years post-injury, provides an unprecedented opportunity to address this possibility and to document recovery-outcome as children move into adolescence and adulthood. Not all children experience problems post-injury. However, predicting individual outcome remains a significant challenge, with particular clinical relevance to treatment and follow-up. Thus, the second aim of the proposed study is to examine factors that contribute to recovery and outcome.Read moreRead less
Mechanisms Of Mechanotransduction In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$253,500.00
Summary
Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have ....Mechanotransduction is the process whereby mechanical stimuli are converted into signals in sensory nerves. This forms the basis of touch, hearing, position sense and many aspects of internal perception. It also constitutes a major component of pain. Our group aims to discover the molecular basis of mechanotransduction in mammals, and in particular how it relates to signaling of events in the digestive system. We and our collaborators have been among the first to explore this question, and have found that three genes are responsible for many aspects of mechanotransduction. Each gene is transcribed to produce a channel or pore in the membrane of sensory nerve fibres which responds to mechanical forces by allowing ions to enter and induce electrical signals. Our early findings in mice with disruption of individual genes indicate that a complex positive and negative interaction of these channels must underlie normal mechanotransduction. However, these channels must represent only a part of the transduction mechanism, with extracellular and intracellular anchors inevitably playing a major role. The identity of such anchoring proteins in mammals is currently emerging, and we are fortunate to have access to mice deficient in specific genes that will provide information about candidates for this role. Through our studies on mechanotransduction in the digestive system in parallel with our collaborators' studies on mechanotransduction in skin we shall not only identify the fundamental mechanisms of mammalian mechanotransduction, but also reveal which components of mechanotransducers are peculiar to the gut. Such peculiarities provide molecular targets for therapy of diseases in which alteration of mechanosensory signaling is itself an aim.Read moreRead less
INVESTIGATING THE VALIDITY OF PRENATAL INSULTS AS RISK FACTORS FOR SCHIZOPHRENIA.
Funder
National Health and Medical Research Council
Funding Amount
$201,100.00
Summary
Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical ma ....Schizophrenia is one of the most devastating of human mental disorders affecting about 1% of the population. The cause of this disorder is not known but it seems certain that it will involve genetic and environmental factors. An adverse environmental factor could be a reduced supply of oxygen and nutrients to a baby during pregnancy. In guinea pigs we aim to investigate whether disruption to the normal supply of oxygen and nutrients to the fetus disrupts the normal fine structure and chemical make up of the brain and gives rise to long-lasting structural and neurochemical changes in adolescent animals, which resemble changes found in the brains of patients with schizophrenia. We will also assess whether behavioural responses of compromised animals are altered in tests that parallel disturbances seen in patients with schizophrenia. Such abnormal brain development could create an underlying vulnerability in the brain, predisposing individuals with risk factors such as genetic inheritance to develop the symptoms of schizophrenia in later life perhaps only after the complete formation of nerve pathways involved in higher brain functioning. If guinea pigs that have been subjected to low oxygen levels during pregnancy show sustained changes in the structure and neurochemistry in regions of the brain that are altered in patients with schizophrenia it would suggest that these long lasting disturbances could result from problems during pregnancy. Thus, this would support the idea that abnormal brain development during pregnancy is one of the underlying causes of schizophrenia.Read moreRead less
Does Maladaptive Remodelling Of The Heart And Vasculature In Response To Preterm Birth Lead To Long-term Cardiovascular Risk?
Funder
National Health and Medical Research Council
Funding Amount
$535,086.00
Summary
Being born prematurely is linked to the development of high blood pressure (a major risk factor for cardiovascular disease) later in life. In this project we will examine whether injury to the cells lining the cardiovascular system and/or structural changes in the wall of the arteries and the heart, as a result of being born early, lead to an elevation in blood pressure and heart dysfunction in adulthood.
Drug-induced Immune Thrombocytopenia: Understanding The Disease Mechanisms Is The Key To Better Treatment
Funder
National Health and Medical Research Council
Funding Amount
$509,550.00
Summary
Many very commonly used medications cause an allergic reaction in a small number of patients that receive them. The allergic reaction results in platelets being destroyed and puts the patients at risk of bleeding. The patient recovers slowly if the drug is stopped but there is no other treatment and no way to reverse the effect quickly if the patient starts to bleed. This project will try to understand the mechanism of the condition and test a potential treatment.
Prenatal Alcohol Exposure: A Molecular Mechanism For Memory Deficits Involving The Zinc-binding Protein, Metallothionein
Funder
National Health and Medical Research Council
Funding Amount
$277,645.00
Summary
Damage to the developing brain is the major social and economic consequence of prenatal alcohol exposure but it is unclear the mechanism by which this occurs. This study will assess whether the maternal zinc-binding protein, metallothionein, causes: 1) alcohol-related cognitive deficits, 2) changes in the expression of alcohol-sensitive cognitive genes. We will further assess whether dietary zinc supplementation throughout pregnancy can prevent alcohol-related anomalies in neurodevelopment.
Is Sympathetic Activation Beneficial Or Detrimental In Septic Shock?
Funder
National Health and Medical Research Council
Funding Amount
$458,755.00
Summary
Septic shock is a major cause of death in intensive care units. It is associated with large increases in sympathetic nerve activity to the heart and kidneys, which have both beneficial and harmful effects. This project will determine the responses to the increased sympathetic activity in septic shock, the causes of it and whether blocking this activation has an overall beneficial effect. This knowledge is essential before drugs that block sympathetic activation are examined in clinical studies.
Novel Approaches To Risk Stratification In Patients With Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$508,838.00
Summary
75% of the mortality in adults with Type 2 diabetes is due to a cardiac event. Early detection and treatment of cardiac disease is paramount in improving health outcomes. An echocardiogram is an accurate and non-invasive identification of cardiac dysfunction. We will assess the prognostic value of echocardiography and novel plasma markers in patients with diabetes. Our results may lead to new management and screening guidelines for heart disease in diabetes.
Cyclic-nucleotide-dependent Regulation Of Axon Guidance Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$527,338.00
Summary
Problems in wiring up the brain underlie several nervous system disorders. The goal of this project is to understand better how this wiring normally forms. This will ultimately lead to a better understanding of what can go wrong with brain wiring, and how to fix such problems. It will also lead to a better understanding of how to make axons regenerate after injury.