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
New And Improved Treatment Strategies For Neonatal Seizures
Funder
National Health and Medical Research Council
Funding Amount
$883,209.00
Summary
Around 10% of neonates in Australia are diagnosed with seizures each year. Seizures worsen neurodevelopmental outcome following hypoxic brain injury. Despite evidence of the limited effectiveness and potential neurotoxicity of current anti-seizure medication, treatment has not changed for many decades. The objective of this study is to optimise treatment of neonatal seizures with a compound that is effective and does not cause harm, or indeed provides neuroprotection for the compromised brain.
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
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
Designing effective learning experiences: Investigating novice and expert teachers’ design processes. Quality teaching leads to quality learning outcomes for students. Primary school teachers are responsible for designing learning experiences for their students in an increasingly complex environment. This project will advance understanding by: characterising and identifying differences in how novice and expert teachers approach the design of learning experiences for their students; capturing exp ....Designing effective learning experiences: Investigating novice and expert teachers’ design processes. Quality teaching leads to quality learning outcomes for students. Primary school teachers are responsible for designing learning experiences for their students in an increasingly complex environment. This project will advance understanding by: characterising and identifying differences in how novice and expert teachers approach the design of learning experiences for their students; capturing expert design processes through practice examples; and investigating how expert practice examples stimulate novice teachers to design learning experiences. This new understanding of teachers' design processes is necessary to enhance teacher preparation and continued professional learning.Read moreRead less
Early career teacher induction: Supporting precarious teachers. This project aims to investigate the ways in which Australian induction policies support precariously employed early career teachers to effectively manage student classroom behaviour. This project expects to generate new knowledge of workforce development and induction experiences of early career teachers employed on casual and short-term contracts. Expected outcomes of this project include alternative policy and practice recommenda ....Early career teacher induction: Supporting precarious teachers. This project aims to investigate the ways in which Australian induction policies support precariously employed early career teachers to effectively manage student classroom behaviour. This project expects to generate new knowledge of workforce development and induction experiences of early career teachers employed on casual and short-term contracts. Expected outcomes of this project include alternative policy and practice recommendations to support the transition of insecure replacement teachers within the profession. The benefits of this research include, improving teachers’ classroom management practices; the retention of new teachers; improving teacher workforce development; and building a healthier education system. Read moreRead less
Investigating the effectiveness of teacher education for early career teachers in diverse settings: a longitudinal study. This project investigates the effectiveness of teacher education programs in Victoria and Queensland in preparing teachers for the variety of school settings in which they begin their careers. The findings will inform state and national policy, as well as the work of professional regulation authorities and teacher education providers.
Intercultural understanding in primary and secondary schools. What facilitates or impedes intercultural understanding in children, adolescents and schools? How can this be addressed? How can we know what makes a difference? This project answers these questions at the individual, school and national level using a novel cultural systems approach and methodological and technological innovations.
Naming the world: early years literacy and sustainability learning. The project seeks to produce knowledge about new forms of literacy emerging in sustainability education. For children born in the 21st century, the enmeshing of natural and human forces in the survival of the planet requires conceptual and practical innovation. Early childhood education can be a fundamental driver in this process. This project aims to integrate literacy and sustainability to produce powerful new learning for you ....Naming the world: early years literacy and sustainability learning. The project seeks to produce knowledge about new forms of literacy emerging in sustainability education. For children born in the 21st century, the enmeshing of natural and human forces in the survival of the planet requires conceptual and practical innovation. Early childhood education can be a fundamental driver in this process. This project aims to integrate literacy and sustainability to produce powerful new learning for young children. It plans to theorise new forms of literacy emerging in sustainability education, articulate innovative pedagogies, and inform national and international policy and practice to address 21st century learning imperatives.Read moreRead less
Supporting teachers and teaching in flexible and non-traditional schools . This project aims to address a critical gap in knowledge about the experiences and conditions of people who teach in flexible and non-traditional schools in Australia. These schools provide a second chance at education for young people with challenging behaviours and/or learning problems. This project expects to generate new knowledge about the experiences and needs of these teachers, using a combination of in-depth resea ....Supporting teachers and teaching in flexible and non-traditional schools . This project aims to address a critical gap in knowledge about the experiences and conditions of people who teach in flexible and non-traditional schools in Australia. These schools provide a second chance at education for young people with challenging behaviours and/or learning problems. This project expects to generate new knowledge about the experiences and needs of these teachers, using a combination of in-depth research methods. Expected outcomes include detailed understanding of support needs for this workforce. This will significantly benefit teachers, sponsors and principals through recommendations on best practice management of this important work, along with evidence-based training artefacts for staff recruitment and retention.
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