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Blood-brain Barrier And White Matter Damage In The Immature Rat Brain Following Systemic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$353,173.00
Summary
Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infecti ....Clinical obstetric and paediatric studies have identified an association between intrauterine infection occurring around two thirds of the way through pregnancy, premature birth and a specific form of damage to the brain of the newborn. This damage mainly affects white matter tracts. These tracts are aggregations of nerve fibres that make the connections between different parts of the brain and may result in cerebral palsy or other neurological disorders. The association between maternal infection and brain damage, one form of which is cerebral palsy, is well established from clinical epidemiological studies, but the biological mechanism of this link is unknown. The CIs' group has recently shown that the condition can be reproduced in neonatal rats at a stage of brain development in the rat that is equivalent to the critical time in human brain development when infection may be associated with brain damage. The CIs' group has shown that an induced inflammatory state similar to a bacterial infection, results in damage to blood vessels in the white matter and is associated with changes in white matter, as occurs in affected babies. The purpose of this study is to understand the nature of the damage to white matter blood vessels and the mechanisms by which materials in blood, which in the normal brain do not pass from the blood to the brain across the blood-brain barrier, are able to do so via the inflammation damaged blood vessels. The study also aims to show whether it is components of the blood entering the brain via the damaged blood vessels that are responsible for the damage to white matter in the immature brain. The outcome should lead to development of ways to improve clinical care of women who acquire infections during pregnancy.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
Compromised Fetal Brain Development: Neurogenesis And The Potential For Therapeutic Intervention.
Funder
National Health and Medical Research Council
Funding Amount
$497,280.00
Summary
Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and ....Lack of oxygen to the fetal brain during pregnancy is thought to be the main causes of brain injury in newborns. Some of these infants will suffer developmental and behavioural problems including cerebral palsy, schizophrenia and epilepsy. Currently, there is no effective treatment to redress these changes in brain development and this is one of the major challenges in perinatal medicine today. We have previously shown in a guinea pig model of chronic placental insufficiency (reduced oxygen and nutrient levels during pregnancy) that there is a reduction in neurons and in the connections between them. This may result from a reduction in number of newly generated neurons (neurogenesis), or an increase in neuronal death (apoptosis), or both. To develop therapeutic strategies to improve brain growth and ultimately functional recovery, we must understand the mechanisms which lead to these brain changes. In this project, we will use our guinea pig model to: 1) determine whether a suboptimal fetal environment decreases neuronal numbers by influencing neurogenesis, apoptosis or both, 2) study changes in the compromised brain environment which are likely to influence apoptosis and neurogenesis, 3) determine whether a suboptimal fetal environment has long-term effects on adult neurogenesis and 4) determine whether treatment with erythropoietin (Epo), a naturally occurring hormone, can resolve deficits in brain development and function. Epo is an exciting candidate as it is, or is in the process of being used to treat stroke and newborn asphyxiation. Epo has also been shown to prevent neuronal death and promote neurogenesis following brain injury. Understanding the mechanisms and finding effective treatments for brain damage is a vital area of endeavour if we are to help infants develop their maximum potential and reduce the enormous social, economic and educational burden which must be borne by the individual and society in general when things go wrong during pregnancy.Read moreRead less
From rehabilitation to recovery after stroke : a model to optimise consumer and carer involvement. The National Research Priorities include 'ageing well, ageing productively'. Within this priority, it is necessary to be inclusive of those who have ongoing disabilities and/or chronic disease. This project aims to facilitate healthy lifestyles and community involvement in a group who have significant barriers to achieving their potential. The high incidence of depression and poor quality of life i ....From rehabilitation to recovery after stroke : a model to optimise consumer and carer involvement. The National Research Priorities include 'ageing well, ageing productively'. Within this priority, it is necessary to be inclusive of those who have ongoing disabilities and/or chronic disease. This project aims to facilitate healthy lifestyles and community involvement in a group who have significant barriers to achieving their potential. The high incidence of depression and poor quality of life in stroke survivors and their carers emphasises the need to enhance wellness in these people. The study will develop a model for promoting recovery and community reintegration in stroke survivors, with the goal of enabling stroke survivors and their carers to actively participate in the community and pursue personal goals.Read moreRead less
Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in ....Epigenetic mechanisms regulating sex differences in fear-related learning and memory. Anxiety disorders represent an enormous burden on society and are associated with premature aging and infertility in men and women. Evidence also indicates that parental anxiety affects child development. Given that fear-related learning has an important influence on emotional health which, in turn, affects lifestyle and the aging process, an understanding of the neural mechanisms mediating sex differences in fear learning will enhance our ability to develop better therapeutic approaches for treating anxiety and preventing relapse, potentially through a gender-specific approach. The studies outlined in this proposal will have implications for promoting and maintaining good health.Read moreRead less
What is normal brain ageing? An investigation of changes in brain structure and cognition in mid-life. Pathological brain changes associated with cognitive decline later in life become detectable in the 40s and sometimes earlier, yet little is known about what constitute normal brain ageing in midlife. Using a number of neuroimaging techniques, this project will develop a detailed map of brain and cognitive ageing in middle-age and their predictors.
The development of the social brain in early childhood. This project aims to understand how the human brain develops social and emotional understanding. The brain has remarkable abilities for understanding our social environment, such as inferring other people’s thoughts and feelings. This project will use neuroscience techniques to investigate how brain networks combine to produce social understanding, how this changes throughout child development, and how it relates to complex social behaviour ....The development of the social brain in early childhood. This project aims to understand how the human brain develops social and emotional understanding. The brain has remarkable abilities for understanding our social environment, such as inferring other people’s thoughts and feelings. This project will use neuroscience techniques to investigate how brain networks combine to produce social understanding, how this changes throughout child development, and how it relates to complex social behaviours. This project’s findings could be used to develop educational programmes that enhance empathy and co-operation, strengthen family relationships, promote social inclusion and reduce maladaptive behaviours. It could also guide intervention in brain disorders that affect social understanding.Read moreRead less
The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will ....The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will be the first to comprehensively advance our understanding of the unique role of sex hormones in shaping the adolescent female brain. It will provide critical understanding of how individual differences in hormonal factors increase risk for emotional problems in females, and inform treatment strategies.Read moreRead less
Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly inc ....Understanding the generation of hypothalamic sleep neurons. This Project aims to investigate the mechanisms controlling the formation of the sleep neurons in the hypothalamus. We all sleep, and normal sleep-wake cycles play a central role in our biology. The functional role of these sleep neurons in the mature brain are well established. However, how the neurons are generated during development is very poorly defined. This project aims to address this critical knowledge gap, and will greatly increase our understanding of how the development of this critical aspect of organismal function is orchestrated during development. This project will also develop bioinformatics tools with broad utility within the biosciences field and enhance the capacity for interdisciplinary international collaborations.Read moreRead less
An Investigation Of The Potential Association Between Sports Concussion And Neurodegenerative Disease In Collision Sports Athletes
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Traumatic brain injury (TBI) is increasingly recognised as a risk factor for dementia. Sports concussion is the mildest form of TBI, but occurs frequently in contact sports, with some players sustaining multiple concussions during their career. Despite the increased attention on this topic, it is not known whether repeated concussions during an athlete’s career lead to a greater vulnerability or a greater risk for dementia later in life. This research program aims to investigate these concerns.