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
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
Carbon Dioxide As A Treatment For Seizures In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$878,389.00
Summary
This study aims to introduce a simple and effective treatment to prevent brain damage from seizures in babies using CO2. Neonatal seizures remain a major clinical problem worldwide and are associated with poor brain outcomes and significant risk of death. Recent trials in human adult epileptics show rapid and effective seizure suppression following the use of CO2. This therapy will significantly impact long-term outcomes for affected babies and reduce the burden of care for families and society.
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
The exposure of infants to adverse events both before and after birth can cause death or permanent disability (eg cerebral palsy) for the infant. Our primary research objective is to minimize the impact and improve outcomes for infants exposed to adverse events before and/or after birth. We will use a multi-disciplinary approach that aims to understand the science and to develop new treatments, thereby representing true “bench to bedside” research.
Enhancing The Neuroprotective Benefit Of Hypothermia With Melatonin In The Asphyxiated Neonate
Funder
National Health and Medical Research Council
Funding Amount
$785,331.00
Summary
During labour, asphyxic episodes which cause a severe reduction in oxygen supply can become prolonged and result in perinatal brain injury, termed Hypoxic Ischemic Encephalopathy, which may underlie cerebral palsy. Presently, newborn infants with suspected encephalopathy are cooled, which modestly protects the brain against cellular injury. We propose that the administration of melatonin to the newborn, in addition to cooling, will decrease the post-asphyxic formation of oxygen free radicals, th ....During labour, asphyxic episodes which cause a severe reduction in oxygen supply can become prolonged and result in perinatal brain injury, termed Hypoxic Ischemic Encephalopathy, which may underlie cerebral palsy. Presently, newborn infants with suspected encephalopathy are cooled, which modestly protects the brain against cellular injury. We propose that the administration of melatonin to the newborn, in addition to cooling, will decrease the post-asphyxic formation of oxygen free radicals, thereby reducing the progression of brain damage.Read moreRead less