Role Of Kynurenine Metabolites In Causing And Preventing Excitotoxic Brain Damage In The Fetus.
Funder
National Health and Medical Research Council
Funding Amount
$92,815.00
Summary
Brain damage is present in some babies at birth, and recent epidemiological and clinical studies strongly suggest that this either occurs some time during the pregnancy, or the conditions are such that the fetal brain is particularly vulnerable to the stresses that are present during labor and birth. In this project we propose that hypoxic (low oxygen) conditions in the womb, either alone or in combination with substances released because of maternal infection, cause accumulation of a neurotoxic ....Brain damage is present in some babies at birth, and recent epidemiological and clinical studies strongly suggest that this either occurs some time during the pregnancy, or the conditions are such that the fetal brain is particularly vulnerable to the stresses that are present during labor and birth. In this project we propose that hypoxic (low oxygen) conditions in the womb, either alone or in combination with substances released because of maternal infection, cause accumulation of a neurotoxic substance - QUINOLINIC ACID - in the fetal brain and circulation. The increased production of QUINOLINIC ACID occurs because certain cells react to the low oxygen and infectious conditions - these cells include MICROGLIA, a cell type in the brain. Little is currently known about MICROGLIA in the developing brain. We will therefore study the effects of hypoxia and infection in fetal sheep, and we will determine how these conditions affect MICROGLIA and the synthesis of QUINOLINIC ACID in the fetal brain. The capacity of the brain to produce QUINOLINIC ACID is closely related to the dietary intake of the essential amino acid TRYPTOPHAN, and it is decreased when synthetic analogues of tryptophan are infused. Therefore, we have devised a treatment regime using these tryptophan analogues to prevent increases of QUINOLINIC ACID concnetrations in the fetal brain, and we propose that a simple treament is at hand to reduce the incidence of perinatal brain damage in human pregnancies.Read moreRead less
International Neonatal Immunotherapy Study (INIS): A Randomised Trial Of Intravenous Immunoglobulin For Neonatal Sepsis
Funder
National Health and Medical Research Council
Funding Amount
$1,151,250.00
Summary
There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routi ....There is promising evidence that treatment of serious infection in babies with a product naturally occuring in blood, intravenous immunoglobulin (IVIG), may reduce deaths by 40% and reduce brain damage in survivors. This would reduce the social, emotional and financial burden of disability on families, health services and society. In financial terms alone, caring for a severely disabled child costs an extra $50,000 per year. However, more evidence is needed before IVIG can be introduced as routine treatment for serious infection in the newborn. The International Neonatal Immunotherapy Study (INIS) is a randomised trial to study the potential benefits of IVIG in 5,000 newborn babies in 150 centres world wide. 26 centres are in Australia and New Zealand, whose expected contribution of 1,500 babies will be vital to the success of the study. INIS is supported by the Commonwealth Government and Australian Red Cross Blood Service, who will oversee the supply and distribution of IVIG, and the NHMRC Clinical Trials Centre, who will coordinate the study. Infants will have a detailed specialist assessment at 2 years of age and a parent questionnaire will be completed, to assess their development. An economic evaluation will be performed to estimate the long-term savings to Australian Health Services and families associated with the IVIG therapy. The IVIG product to be used in Australia is Intragam P, manufactured by CSL, who have an unrivalled safety record. CSL has been making IVIG since 1989 and no transmission of HIV or hepatitis viruses has ever been reported. CSL estimate the risk of transmission of these viruses by IVIG is under 1 in 10 million treatments. INIS will provide reliable evidence about IVIG, a treatment with minimum known risk that may benefit thousands of Australian children and millions more worldwide.Read moreRead less
Novel Approaches To Assessing Cerebral Circulation And Oxygenation In Preterm Human Infants.
Funder
National Health and Medical Research Council
Funding Amount
$489,145.00
Summary
In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in t ....In the first few days after birth, some premature babies develop low blood pressure. It is thought that this meant that the amount of blood and oxygen going to the brain would also fall. If blood pressure became very low, this could injure the brain. Drugs are used to prevent low blood pressure, but their effect on blood flow and oxygen in the brain is uncertain. This study aims to develop simple cotside monitoring procedures that allow neonatologists to monitor oxygen supply and blood flow in the brain in tiny babies who weigh less than 1000gm, and what happens within the brain when drugs are given to raise blood pressure. We will employ a new instrument that generates low intensity near infrared light which passes safely into the brain and is absorbed according to the amount of oxygen present in very small blood vessels. As the methodology is new, we intend to first validate the measurement in immature lambs. The instrument will then be applied in studies of babies undergoing intensive care and at risk for low pressure and brain injury, as many as 5000 babies each year in Australia.Read moreRead less
Neonatal Cranial Ultrasound: Safety, Knowledge And Practice Of Prolonged Or Repeated Exposure To Acoustic Waves
Funder
National Health and Medical Research Council
Funding Amount
$255,055.00
Summary
Ultrasound is routinely used for diagnosis of brain lesions amongst newborns. Animal studies have shown that ultrasound can sometimes be harmful to the brain. We currently have very little information on the characteristics of neonatal cranial scans. This project will investigate current knowledge of safety and training via a nationwide survey, analyse the elements of 'typical' scans and measure brain surface heating after ultrasound amongst neonates.
Genes Important For Early Brain Development Are Also Important For Adult Brain Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,346.00
Summary
I committed to understanding of how the brain develops, grows and regenerates. My laboratory is active in finding a cure for brain injury following brain trauma or brain ischemia. I have discovered that the genes that drive neuron migration and wiring in the fetus also function in the adult brain to improve neuron survival and regeneration. Probing the function of these genes will deliver twin benefits in preventing brain disorder in the newborn and treating brain disease in the adult.
Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertake ....Newborn babies are at risk of becoming short of oxygen during delivery and sustaining brain damage. Seizures may cause further damage to the brain because they release damaging chemicals or make extra energy demands on the brain that cannot be met. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain. We are proposing to automatically detect and count seizures, building upon 8 years of fundamental EEG signal processing research work we have undertaken. We anticipate that the product will be of major commercial interest. We will further explore what is a rapidly expanding marketplace and ensure we maximize the commercial return on this product.Read moreRead less
Mechanisms Of PTEN Regulation By Ndfip1 And Their Biological Consequences For Neuron Survival During Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$686,640.00
Summary
We have discovered a new protein (Ndfip1) that protects brain cells from death after brain injury from trauma and stroke. We will investigate why this protein is activated only in some, but not in other, brain cells after injury. In this application, we will study the mechanisms behind neuron protection, and use this information to explore how to increase the number of brain cells activating Ndfip1.
FETAL BRAIN INJURY RESULTING FROM INTRAUTERINE INFECTION: LONG TERM CONSEQUENCES AND THE POTENTIAL FOR INTERVENTION
Funder
National Health and Medical Research Council
Funding Amount
$452,640.00
Summary
Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. Unfortunately, at present, it is not possible to prevent or effectively treat brain damage in the fetu ....Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. Unfortunately, at present, it is not possible to prevent or effectively treat brain damage in the fetus or newborn, partly due to ignorance about how and when the damage is occurring. In recent years it has become evident that infections in the mother, may be linked to both premature birth and brain damage. It has been proposed that the certain chemicals (cytokines) which are released during an infection can across the placenta to the fetus, causing inflammatory changes that lead to brain damage. However, although associations have been shown in studies of women, there is little evidence that infections actually cause brain damage in the fetus. This project will define the effects of an inflammation inducing chemical (bacterial endotoxin) on the fetal brain and the pattern of inflammation it sets up in the fetus. We will also examine the effects of brain damage caused by endotoxin in the newborn lamb, and relate this to alterations in behaviour. Once we have defined the effects of endotoxin on brain structure, we will test the effects of chemicals that are known to block the actions of inflammatory cytokines. We hope that by blocking the chemical pathway that leads to the production of harmful cytokines we may be able to prevent brain injury from occurring when the fetus is exposed to an infection in the mother. It is expected that this project will provide important information that helps us to understand how infection in the mother can cause brain injury in the fetus. This information is vital if strategies to prevent or treat brain injury are to be developed.Read moreRead less
Emotion Regulation After Brain Injury: New Approaches To Remediation
Funder
National Health and Medical Research Council
Funding Amount
$922,662.00
Summary
Traumatic brain injuries, often from motor vehicle accidents, devastate the lives of thousands of young Australians each year and can lead to changes in personality and emotional regulation. Frontal lobe damage may cause apathy, withdrawal and loss of motivation or a loss of control leading to poor inhibition and anger outbursts. In this project we trial some experimental approaches to improving emotion regulation including biofeedback, self-control therapy and direct cortical stimulation.