Perinatal Stress Leads To Neurosteroid Deficits And Adverse Behavioural Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$1,198,042.00
Summary
This grant will examine the effect of psychosocial stress experienced after birth on the production and regulation of steroid hormones in the brain of newborn animals. The work will investigate how stress changes the levels these brain steroids and sensitivity to them and if these effects are remain into adulthood. The studies will then determine if these changes lead to adolescent behaviour disorders. The effectiveness of steroid therapies in treating these disorders will also be determined.
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
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
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
Organizational Change And Treatment Of Depression And Dementia In Aged Care Facilities
Funder
National Health and Medical Research Council
Funding Amount
$567,052.00
Summary
Mental health disorders are common in aged care settings. However, these problems are not well managed. This situation results in distress for residents and family members, as well as high levels of burnout and turnover among staff. This project will address the organizational barriers with the aim of better managing and treating depression and behavioural problems associated with dementia.
Telehealth In Residential Aged Care Facilities: Improving Access To Specialist Care
Funder
National Health and Medical Research Council
Funding Amount
$972,606.00
Summary
People in long term residential care have complex and chronic care issues. The staff may be able to provide more focused care if they have the support of specialists for advice on the care of residents. This project considers the value of a geriatric specialist assessment for all new residents via video conferencing, directly to the residential care facility. This will be supplemented by access to a wide range of other specialists coordinated through a telehealth service model on an "as needs" b ....People in long term residential care have complex and chronic care issues. The staff may be able to provide more focused care if they have the support of specialists for advice on the care of residents. This project considers the value of a geriatric specialist assessment for all new residents via video conferencing, directly to the residential care facility. This will be supplemented by access to a wide range of other specialists coordinated through a telehealth service model on an "as needs" basis.Read moreRead less
Does Caffeine Affect The Development Of The Very Immature Brain: Dose Response Relationship?
Funder
National Health and Medical Research Council
Funding Amount
$668,386.00
Summary
Premature birth is a major health problem worldwide. Preterm babies often develop apnoea of prematurity (AOP), which is commonly treated with caffeine. Trials indicate that preterm babies treated with low dose caffeine have less neurodevelopmental disabilities at 18 months. Higher doses of caffeine are often needed to reduce AOP but the risk of this is unknown. We will study the short and long-term effects of increasing doses of caffeine on the developing brain in a long-gestation species.
Building On Our Strengths (BOOSt): Developing And Evaluating Birthing On Country Primary Maternity Units
Funder
National Health and Medical Research Council
Funding Amount
$1,090,701.00
Summary
Optimal healthcare during the year before and after birth can provide benefits for a lifetime. Our project will deliver this optimal care by implementing and evaluating Birthing on Country Service Delivery Models in urban, regional and remote sites. Birthing on Country combines Indigenous knowledge and governance, culturally safe care, continuity of midwifery carer, birth in an Indigenous birth centre and development of the Indigenous maternal and infant workforce.
The Australian Maternity Outcomes Surveillance System: Improving Safety And Quality Of Maternity Care In Australia
Funder
National Health and Medical Research Council
Funding Amount
$820,438.00
Summary
There is currently no Australian system of monitoring severe complications of pregnancy. Many of these complications are rare, making them difficult to study and limiting knowledge as to their true frequency, cause and best treatment. We intend to introduce a national reporting system- Australian Maternity Outcomes Surveillance System which would provide the research structure to study these rare conditions, thus aiming to improve the safety and quality of maternity care provided in Australia.
Partnership Centre: Dealing With Cognitive And Related Functional Decline In Older People
Funder
National Health and Medical Research Council
Funding Amount
$12,500,000.00
Summary
The focus of this Partnership Centre is how to better apply our existing knowledge and how to create new knowledge that will directly improve support to those elderly suffering from cognitive decline, their carer’s (formal and informal) and the various agencies delivering services for them. This Partnership Centre’s Investigator Team will engage in a range of activities to improve aged care service planning (including continuity of care and risk assessments of community care); develop and implem ....The focus of this Partnership Centre is how to better apply our existing knowledge and how to create new knowledge that will directly improve support to those elderly suffering from cognitive decline, their carer’s (formal and informal) and the various agencies delivering services for them. This Partnership Centre’s Investigator Team will engage in a range of activities to improve aged care service planning (including continuity of care and risk assessments of community care); develop and implement new approaches to support informal carer’s; reduce stigma around cognitive decline in both the health care and community context; improve the size and quality of the aged care workforce; assist with decision making, rights, citizenship and related ethics through education; improve aged care regulation; promote responsible medication management; develop and disseminate up-to-date clinical guidelines; and implement proven models of care.Read moreRead less