Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or ....Newborn babies are at risk of becoming short of oxygen during delivery. Death or brain damage may result. In the days after birth, when the brain is attempting to recover from the lack of oxygen, seizures (also called fits) are common. Seizures may cause further damage to the brain because they release damaging chemicals such as glutamate or because they make extra energy demands on the brain that cannot be met. It is difficult to be certain whether unusual movements or twitches are seizures or not. To detect seizures, it is necessary to measure the EEG, the tiny electrical signals from the brain that can be measured from the scalp using small stick on electrodes. It is difficult to measure EEG, particularly for longer periods, because the electrodes may fall off, the baby may move excessively or electrical interference may ruin the recording. We are proposing to measure EEG for 48 hours in babies who have suffered a lack of oxygen during delivery. We will develop, optimise and implement a new method of automatically detecting seizures, building upon 6 years of fundamental signal processing research work that we have done in the newborn. We will test this system against the 'gold standard' to determine how accurate it will be in detecting seizures. We will also try to find out whether damage in particular areas of the brain or in particular cell types within the brain is most likely to be associated with seizures. The anticipated outcome is that we will be able to accurately identify seizures. This is a major step on the path to being able to prevent injury to the brain and to monitor the effectiveness of new experimental treatments.Read moreRead less
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.
I am a perinatal paediatrician undertaking clinically-focussed research on brain development, brain disorders, brain therapies, neurodevelopmental outcomes and the development, application and evaluation of new technology to clinical problems.
Using Astrocytes To Protect The Brain From Injury: Investigating Mechanisms And Therapeutic Strategies.
Funder
National Health and Medical Research Council
Funding Amount
$374,310.00
Summary
Brain damage caused by hypoxia (lack of oxygen) is a common problem in babies and can lead to outcomes ranging from cerebral palsy to death. We have a limited understanding of the mechanisms that cause damage, and thus very limited treatments. This project will investigate the role of cells called astrocytes in brain injury and identify novel therapeutic strategies to prevent or reverse brain damage. The outcomes of this research will ultimately lead to new treatments for hypoxic brain injury.
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.
Neurosteroid Mediated Protection After Birth: Approaches For Maximising Protective Steroid Levels In The Neonatal Brain
Funder
National Health and Medical Research Council
Funding Amount
$450,703.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the ....Complications during pregnancy, birth asphyxia or premature birth can lead to neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neurosteroids are a group of steroids that regulate brain activity. These steroids protect brain cells from damage caused by an inadequate supply of oxygen by suppressing toxicity caused by excessive activity. We have shown that the levels of these protective steroids are remarkably high in the fetal brain and levels rise further in response to fetal stress. The placenta contributes steroid precursors that help maintain these high neurosteroid levels. This placenta-fetal brain interaction comprises an internal mechanism that protects the fetal brain from adverse events during pregnancy. At birth, however, there is a dramatic decline in neurosteroid concentrations in the brain after the loss of the placental precursor supply. The fall in concentrations is even greater in animals that are born growth restricted. This suggests that newborns, particularly those from compromised pregnancies, are at increased risk of brain damage due to low neurosteroid levels. We believe that certain commonly used steroid therapies may also lower steroid levels in the brain and result in increased vulnerability to brain damage during birth or in the early neonatal period. Alternatively, we propose that replacement of neurosteroid precursors in the newborn may raise brain neurosteroid levels and protect against brain damage. In the proposed studies we will evaluate treatments that can raise the concentration of steroids and determine the best strategy for reducing brain injury following complications during pregnancy, at birth and during the early newborn period. This work will determine the best therapeutic approaches for maximising neurosteroid-induced brain protection and for reducing the risk of brain damage.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
Neuroactive Steroids In The Developing Brain: Potential For Preventing Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown tha ....Complications during pregnancy, birth asphyxia or premature birth can lead to serious neurological impairment in the newborn. Despite excellent neonatal care many of these babies go on to have serious handicaps. Neuroactive steroids are a group of neuromodulators that are derived from the hormone progesterone. These steroids fall into two groups, those that appear to protect brain cells from damage caused by an inadequate supply of oxygen and those that may increase cell death. We have shown that protective neuroactive steroids are present in very large amounts in the fetal brain. Steroids produced by the placenta are converted to these neuroactive products by enzymes in the brain leading to the high levels that are seen during fetal life. Certain adverse conditions during pregnancy as well as preterm birth may cause marked changes in the balance of steroids that could increase susceptibility to brain injury. We have found that areas of the brain, where damage most often occurs, normally contain the highest amount of protective steroids, but only in late pregnancy. This suggests that disturbances that lower steroid production in these areas could contribute to the death of cells, particularly in mid-pregnancy and after premature birth. In the proposed studies, we will examine whether a toxic balance of steroids develops following adverse events in pregnancy as well as the areas of the brain where this is most pronounced. We will examine the changes in the expression of enzymes that can potentially cause the accumulation of protective steroids in the brain. We will then examine treatments that can raise the concentration of steroids and determine which combination of steroids best reduces cell death and brain injury following complications during pregnancy. The findings of this work will indicate the best therapeutic approach that may be adopted to modify the concentration of certain steroids so as to reduce the risk of brain damage in the fetus and neonate.Read moreRead less
Evaluation Of Combined Mild Hypothermia And Magnesium As A Neuroprotective Therapy Following Cerebral Ischaemia/stroke
Funder
National Health and Medical Research Council
Funding Amount
$310,286.00
Summary
Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annuall ....Stroke-cerebral ischaemia affects over 50,000 Australians every year and is Australia's leading single cause of disability and third greatest cause of death after heart disease. About 25% of people who suffer a stroke die within one month while most survivors are disabled because of impaired speech, memory, thought processes, vision, balance, or motor control of the limbs (paralysis). The direct and indirect cost of stroke-cerebral ischaemia to the Australian community is over $2 billion annually. The ability to inhibit or limit brain damage once a stroke has occurred will reduce the devastating effects of stroke to patients and the Australian community. Despite decades of research, there is no totally satisfactory drug that directly inhibits brain damage following stroke; the search for new treatments is paramount. A stroke occurs when there is a reduced blood supply to the entire brain (global cerebral ischaemia; eg. cardiac arrest, closed head injury) or to a specific region of the brain, usually as a result of a blockage in a brain artery (focal cerebral ischaemia or thrombo-embolic stroke). This project will evaluate the efficacy of combined magnesium and mild hypothermia (35) treatment protocols to reduce brain damage in animal models of focal and global cerebral ischaemia. This work stems from our recent data showing for the first time that magnesium is only neuroprotective in animals following cerebral ischaemia when present with hypothermia. Thus our data indicates that magnesium, when combined with hypothermia is an effective stroke therapy. Moreover treatment with magnesium-mild hypothermia has several attractions. Both are likely to have multiple mechanisms of action, are cheap to administer and safe. Importantly, the experimental findings from this project will enable better design of future clinical trials to test the efficacy of combined magnesium-modest hypothermia to improve patient outcome following stroke.Read moreRead less