Contribution Of Disturbed Blood Flow And Cerebral Metabolism To White Matter Damage In The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$369,375.00
Summary
It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral ....It has been known for some time that the white matter regions of the developing brain are particularly vulnerable to damage. These regions are deep in the brain near the ventricles, and are rich in myelin sheaths wrapped around the nerve fibres running from cell-rich areas in the outer layers of the brain to other regions, and down into the spinal cord. Damage to white matter usually leads to behavioural, learning and motor problems in the newborn infant - in its severest form, seen as cerebral palsy. Such outcomes are often associated with the presence of asphyxia and infection during pregnancy, leading to the belief that the damage first arises while the baby is still in utero. In this application we suggest that asphyxia and-or infection during pregnancy cause prolonged disturbances in the regulation of blood flow and integrity of the blood-brain barrier in the developing brain, together with changes in metabolism that result in accumulation of prostaglandins and the toxic hydroxyl radical, leading irreversibly to cell death. If this series of events proves to be true, we have suggested and will test several protocols for protecting the fetal brain, which should be readily translatable to clinical practice.Read moreRead less
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
Birth is one of the greatest physiological challenges that we will ever experience and so it is not surprising that it is a period of high risk of death. Despite the risk, our understanding of how infants transition from fetal to newborn life is limited. My research is focused on improving our understanding of how infants make the transition at birth so that we can reduce the risks for these most vulnerable of humans. In particular, I want to improve outcomes for infants born very premature.
Pathways Of Neurosteroid-mediated Protection Following Compromised Pregnancy And Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$565,785.00
Summary
The hormonal environment of pregnancy is essential for normal development of the fetal brain. Levels of key hormones fall following premature birth and are further suppressed if the fetus is small or subjected to stress. This leads developmental problems in infants from the pregnancies. This project will examine effectiveness of replacement and supplementation treatments with critical neurosteroid hormones in reversing the adverse neurological effects of these complications of pregnancy.
Extracellular Acidosis And PH-modulating Drugs As Novel Therapies For Neuroprotection In Hypoxia/ischemia In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$452,310.00
Summary
Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related br ....Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related brain damage in babies. This study brings together a multi-disciplinary team driven by the clinical need to develop suitable strategies for neuroprotection in the developing brain. We will investigate the neuroprotective properties of the clinically relevant factor of acidosis and determine how acidosis influences neuroprotectant drugs. In the future, it is envisaged that this study will lead to rationally-based clinical trials aimed at improving neurodevelopmental outcomes for babies who suffer asphyxia and for infants who are victims of near-drowning or head trauma.Read moreRead less
Preventing Prenatal Brain Injury In Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$511,294.00
Summary
Intrauterine fetal growth restriction (IUGR) is a serious complication of pregnancy associated with increased perinatal morbidity and mortality. In particular, IUGR infants have a high risk of perinatal brain injury which is likely to arise from damage before birth. Our aim is to use an ovine model of IUGR to define the causes of that brain injury and to develop new therapies that could be offered to women to protect their unborn baby.
Cerebrovascular Effects Of Intrauterine Hypoxia: Contribution To Perinatal Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$579,138.00
Summary
During pregnancy, delivery of oxygen and nutrients to the growing fetus is sometimes disturbed, and can lead to injury of the developing brain. In this project we investigate the idea that low oxygen (hypoxia) causes brain demage to blood vessels in the fetal brain, and new blood vessesl produced in an attempt to repair this damage are fragile and prone to rupture, explaining the high incidence of bleeding in the brain of prematurely-born and full term infants that experience birth hypoxia.
Potential For Creatine Or Melatonin As Dietary Supplements In Pregnancy To Prevent Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$483,217.00
Summary
Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy su ....Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy such as infection, preterm birth, or fetal growth retardation. In this project we propose that providing extra amounts of the dietary constituent creatine, or of the hormone melatonin, to the pregnant animal in late gestation, will provide NEUROPROTECTION to the developing brain in the face of an asphyxial challenge that otherwise causes damage. We will use pregnant sheep to investigate the effects of asphyxia in utero on the fetal brain using techniques that allow us to monitor metabolic changes within the brain in real time. In addition, we will use the pregnant Spiny Mouse to investigate the effects of birth asphyxia on the postnatal brain structure and behavioral development. We will study groups of animals fed a normal diet, and compare then to animals that receive additional amounts of creatine or melatonin. We expect to determine if either of these treatments have the potential to protect the developing brain from asphyxial damage, and to recommend if similar treatments could be used in pregnant women where the obstetrician suspects the baby's brain is at risk of damage.Read moreRead less
Neurodevelopmental Outcomes After Novel Interventions In Newborn Infants
Funder
National Health and Medical Research Council
Funding Amount
$188,226.00
Summary
Children who were sick in the newborn period or born preterm are at increased risk of abnormal development, particularly problems with their ability to walk, think and learn. This research will assess how new treatments affect sick newborns’ later development. For example, giving preterm babies healthy germs, or probiotics, decreases a serious bowel infection, called necrotising enterocolitis or NEC. This research will find out if they also help preterm brain development when the children are 2 ....Children who were sick in the newborn period or born preterm are at increased risk of abnormal development, particularly problems with their ability to walk, think and learn. This research will assess how new treatments affect sick newborns’ later development. For example, giving preterm babies healthy germs, or probiotics, decreases a serious bowel infection, called necrotising enterocolitis or NEC. This research will find out if they also help preterm brain development when the children are 2 years old.Read moreRead less