Early Identification Of Infants Who Will Benefit From Neural Rescue Treatment
Funder
National Health and Medical Research Council
Funding Amount
$206,320.00
Summary
Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the exte ....Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the extent of disabilities suffered by these children. The same treatments may also be helpful in children following near drowning and head trauma. Neural rescue therapies must be applied less than 24 hours following the event which has caused the reduction in oxygen supply. Thus, before these treatments can be tested, it is necessary to find a way to quickly tell which babies may benefit from the treatments. This study will trial a new method which is inexpensive and can be used without moving the baby away from its incubator. This technique involves a new application of an established technology to detect the redistribution of water within the brain one of the earliest signs of impending brain cell death. The research team consists of medical personnel from the intensive care nurseries of both the Royal Women's Hospital and the Mater Mother s Hospital, as well as scientific staff experienced in the use of this technology. If this technique is effective, it will enable babies to receive maximum benefit from new treatments and reduce long-term difficulties suffered by these children and their families.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
Enhancing The Cardioprotective Effect Of Diadenosine Tetraphosphate: Designing Inhibitors Against Ap4A Hydrolase
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitocho ....Ischemia describes the condition where blood flow in the blood vessels of the heart is decreased or blocked, preventing delivery of oxygen and nutrients to the heart. Ischemic preconditioning is a phenomenon where short bursts of ischemia, followed by reperfusion, actually protect the heart from a subsequent longer period of ischemia. The biochemical signalling events involved in preconditioning are complex and incompletely defined, but most likely involve multiple pathways, although the mitochondrial ATP-dependent potassium channel may be in common with most pathways. Pretreatment with the compound diadenosine tetraphosphate (Ap4A) mimics ischemic preconditioning with noticeable reductions in tissue necrosis (cell death). This treatment has been shown in experimental work to protect the heart during periods of stress such as in heart surgery or recovery from an ischemic event. The biological site of action by Ap4A may be the mitochondria ATP-dependent potassium channel or an associated protein. Ap4A can be degraded by enzymes located inside and on the outside of heart cells, notably by two forms of Ap4A hydrolase. We will use antibody assays to understand the specific localization and amount of Ap4A hydrolase before and after ischemia and after ischemic preconditioning in human heart muscle and blood vessels. We propose to determine the structure of the enzyme and use novel computer methods to screen databases for potential inhibitors. These inhibitors of Ap4A hydrolase activity could aid the design of a potent inhibitor that would prevent Ap4A hydrolase from degrading Ap4A and therefore enhance the cardioprotective properties of Ap4A as well as minimizing side effects from the break down of Ap4A. We will also use these inhibitors and other known non-degradable Ap4A analogues in bioassays to test the relative significance of Ap4A hydrolase present in different cellular locations.Read moreRead less
Preventing Adverse Outcomes Of Neonatal Hypoxic Ischaemic Encephalopathy With Erythropoietin: A Randomised Controlled Multicentre Australian Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,103,844.00
Summary
One in five babies die worldwide from Hypoxic Ischaemic Encephalopathy caused by low oxygen or blood supply to the brain around birth. Survivors often have low IQ, cerebral palsy, epilepsy or autism. Cooling the baby after birth (hypothermia) reduces the severity of brain damage, but half still die or are disabled. This randomised, controlled trial will test whether Erythropoietin (a natural hormone) can further protect and repair these babies' brains, saving lives and preventing disability.
Stem Cell Treatment For Neonatal Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$954,195.00
Summary
Hypoxic-ischaemic encephalopathy occurs when the fetus receives inadequate oxygen in labour and many babies die or have brain damage. Stem cell therapy might save these babies from brain damage but there are many unknowns, such as which stem cells to use and how many. Through our skills in stem cells and measuring the rescued brain following injury, we will determine the necessary details for the most effective stem cell therapy to be ready to immediately test the treatment in a RCT in babies.
Protecting Newborn Brains Via Innovative Monitoring Technology
Funder
National Health and Medical Research Council
Funding Amount
$394,460.00
Summary
This project aims to develop innovative brain monitoring technology which could help minimise brain damage in newborn babies with brain injuries, thereby delivering a healthier start to life. Such novel technology may automatically analyse babies’ brain activity and deliver instant detection of critical abnormalities, which could enable more effective treatment of brain injuries. Babies with reduced oxygen or blood supply to the brain and premature babies could benefit from such innovations.
GABA Excitotoxicity, Neuroprotection And The Perinatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Approximately 3.5% of babies die each year from brain damage due to perinatal asphyxia, a shortage of oxygen to the developing brain. Babies that survive face lifelong neurological disabilities, placing enormous burden on health, social and economic resources. Current treatments are inadequate. We will examine what occurs when there is a shortage of oxygen to the developing brain and investigate pathways to hypoxic brain injury that offer opportunities for therapeutic intervention.
The Potential Of Cord Blood Stem Cells To Reduce Neuroinflammation
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Cerebral palsy (CP) is the most common cause of physical disability in children and it is well recognised that the brain injury that underlies CP occurs during pregnancy or around the time of birth. Stem cells isolated from umbilical cord blood offer a promising new therapy for children with CP. This proposal will explore the mechanism of how cord blood stem cells can reduce brain inflammation and damage caused by hypoxia-ischemia, an event known to lead to cerebral palsy.
A Randomised Controlled Trial Of Whole Body Cooling On The Outcome Of Term Infants With Hypoxic Ischaemic Encephalopathy
Funder
National Health and Medical Research Council
Funding Amount
$386,732.00
Summary
The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from ....The aim of this project is to investigate whether the brain damage caused by a serious lack of oxygen around the time of birth can be prevented or reduced by cooling the baby's temperature to 34C for 72 hours. The consequences, of a lack of oxygen, to the brain, around the time of birth can be devastating. Over 30% of those babies with abnormal brain function soon after birth either die or survive with severe permanent brain damage. There is no specific treatment for these infants. Evidence from studies in animals, as well as human adults and a small number of newborn infants, suggests that moderate body cooling started soon after birth in babies with serious abnormal brain function might prevent or reduce brain damage. This project is a multicentre trial, where infants who have suffered from a severe lack of oxygen around birth, are randomised to body cooling to 34C for 72 hours. This will be started as soon as possible after birth at their hospital of birth. If the baby needs to be transported this will be started when the newborn transport team collects the baby for transfer to a newborn intensive care unit. This new treatment will be compared with maintaining the baby's temperature at 37C. This project will investigate a new, simple and pragmatic treatment that might reduce brain damage. If it finds that cooling infants who have been severely deprived of oxygen is an effective and safe treatment, the information will be applicable to any of the very large number of babies around the world who suffer from a serious lack of oxygen around the time of birth.Read moreRead less