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
The role of P2X7 and P2X4 receptor mediated innate phagocytosis in pathogenesis and treatment of neurodegenerative diseases. This project will identify how inherited variation in two proteins of the brain can accelerate the removal of neurones and predispose to a range of neurodegenerative diseases. Knowledge of the biological basis of this finding will allow a search for new compounds which will slow and protect against this form of neurodegeneration.
Investigating Mechanisms Of Axonal Pathology Following Oligodendrocyte Apoptosis: Avenues For Neuroprotection In Early MS
Funder
National Health and Medical Research Council
Funding Amount
$678,138.00
Summary
Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal functio ....Recent research suggests that Multiple Sclerosis could first be triggered by the death of a type of brain cell called an oligodendrocyte. These cells insulate nerve cells in the brain which help them function normally. We will test the idea that death of oligodendrocytes impairs nerve cell function by causing inflammation and by depriving nerve cells of energy. We will determine whether preventing inflammation and feeding the nerve cells an alternative source of energy can restore normal function.Read moreRead less
Do The Developmental Vitamin D-deficiency And Maternal Immune Activation Animal Models Of Schizophrenia Have Convergent Early Pathways ?
Funder
National Health and Medical Research Council
Funding Amount
$669,580.00
Summary
The etiology of schizophrenia is unknown but it is generally considered to have a neurodevelopmental basis and involve altered dopamine signaling. Using two distinct developmental animal models of schizophrenia we have shown convergent gestational abnormalities in how dopamine systems develop. This is possibly a convergent early etiological mechanism in schizophrenia.
Physiology of tau protein: a novel role in scaffolding and intracellular distribution. Understanding brain function remains a challenge. This project will study the normal role of the Alzheimer's disease-related protein tau in brain function during ageing. This will significantly enhance current understanding of brain function.
Investigating the intercellular trafficking of proteins and RNA and its relevance to neurodegenerative diseases. Alzheimer's and prion diseases are neurodegenerative disorders associated with protein misfolding. This project brings together similar features of these diseases using novel cell- and animal-based studies to develop a greater understanding of the molecular basis of these disorders.
The Role Of Innate Immune Memory In The Transition From Acute To Chronic Pain
Funder
National Health and Medical Research Council
Funding Amount
$331,440.00
Summary
Chronic pain costs Australians more than $34 billion annually and is the 3rd highest Australian disease burden. It has long been thought to be a disease of the wiring of the brain. This project aims to challenge this long held belief by examining the impact of the immune system in creating chronic pain. Such work promises to provide new and better ways to prevent chronic pain, which will improve & maintain good health for all Australians.
Toll Like Receptor signalling as a mediator of sex differences in pain, opioid and alcohol action. Brain immunology will be examined in this project to see if the signalling of a receptor called Toll Like Receptor 4 can explain sex differences in pain, and the action of pain killers and alcohol. These findings will have significant implications on the understanding of male and female brains, and will assist in the design of new drugs to treat brain and spinal cord diseases.
Harnessing non-invasive brain stimulation to improve language function in healthy and pathological ageing. This project will examine how the ability of the ageing brain to process language can be improved by non-invasive brain stimulation. The findings have the potential to reveal new ways to treat language impairments in ageing-associated brain injury and disease.
Discovery Early Career Researcher Award - Grant ID: DE180101075
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understandin ....Novel immune cell subsets in the centre nervous system and supporting tissues. This project aims to identify and characterise novel resident immune cell subsets within the brain and retina, and their close supporting tissues. The project expects to generate new knowledge in the areas of neuroimmunology and ocular immunology by using molecular and cellular techniques to examine the diversity of immune cells within the brain and retina. It is expected that the project will advance our understanding of the biological mechanisms that protect the central nervous system from harmful inflammation and thus improve our knowledge of the immunobiology of the brain and eye.Read moreRead less