Delayed Radial Glial Maturation Linked To NFI Deficiency As An Underlying Cause Of Cortical Defects In Humans And Mice
Funder
National Health and Medical Research Council
Funding Amount
$801,979.00
Summary
The timely generation of neurons and glia is important for brain development and consequently brain function throughout life. Nuclear factor I (NFI) genes are important for regulating the production of neurons and glia, and people with disrupted NFI genes have severe cognitive and motor deficits. Using human genetic data and mouse models, we will analyse how disrupting these genes affects brain development, and changes the overall structure and wiring of the cerebral cortex as well as behaviour.
Targeting Of Callosal Axons To Duplicate Cortical Areas In The Contralateral Hemisphere
Funder
National Health and Medical Research Council
Funding Amount
$600,785.00
Summary
The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain ....The two sides of the brain communicate via a large fibre tract called the corpus callosum. This proposal investigates how the corpus callosum is formed during embryonic and postnatal development. Specifically, we investigate how the axons that make up the corpus callosum are able to locate their precise target in the contralateral hemisphere so that the brain circuit they form will be functional. We have developed a new mouse model to discover the fundamental mechanisms regulating how the brain is wired in order to function correctly.Read moreRead less
Guidance Mechanisms Regulating The Development Of Axonal Projections From The Cingulate Cortex.
Funder
National Health and Medical Research Council
Funding Amount
$484,236.00
Summary
The corpus callosum is the largest fibre tract in the brain and connects neurons in the left and right cerebral hemispheres. A subpopulation of callosal axons arise from neurons in the cingulate cortex and are the first to cross the midline. Defects in activation or wiring of the cingulate cortex are strongly implicated in acute pain, schizophrenia and bipolar disorder. This proposal investigates how the commissural projections of the cingulate cortex become wired up during development.
Cellular And Molecular Regulation Of Interhemispheric Fusion
Funder
National Health and Medical Research Council
Funding Amount
$449,489.00
Summary
In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the ....In the developing brain, the two cerebral hemispheres undergo interhemispheric fusion to allow commissural fibres to cross the midline. Lack of interhemispheric fusion results in agenesis of the corpus callosum and may manifest as an interhemispheric cyst in acallosal patients. This project will investigate the cellular and molecular mechanisms that regulate interhemispheric fusion, including removal of the leptomeninges, astroglial differentiation and the formation of adherens junctions at the interhemispheric fissure to mediate fusion.Read moreRead less
Astroglial Remodelling Of The Interhemispheric Midline Is Regulated By Deleted In Colorectal Cancer (DCC) Signalling And Is Required For Corpus Callosum Formation
Funder
National Health and Medical Research Council
Funding Amount
$669,400.00
Summary
The integration of information between the brain hemispheres occurs via a large bundle of connecting nerve fibres called the corpus callosum. People with a genetic mutation in DCC display mirror movement disorder and some have a severe brain defect where the corpus callosum fails to form, but at present we don’t understand the function of this gene. In this study we will investigate how DCC functions in early brain development to regulate corpus callosum formation and mirror movement disorder.
Molecular And Activity Dependent Mechanisms Regulating The Targeting Of Corpus Callosum Axons In The Contralateral Hemisphere.
Funder
National Health and Medical Research Council
Funding Amount
$413,266.00
Summary
The brain is made up of circuits of neurons that process specific information. For example, the somatosensory cortex receives and sends connections to other somatosensory areas, including the contralateral cortex, but how these systems are wired up is not known. We will investigate whether information about the size and position of the cortical areas and activity-matching of the somatosensory information received by each hemisphere are used to guide callosal axons to their targets.
REACH: Randomised Trial Of EArly Rehabilitation In Congenital Hemiplegia
Funder
National Health and Medical Research Council
Funding Amount
$972,777.00
Summary
Infants with asymmetric brain lesions are at high risk of congenital hemiplegia. This study compares modified CIMT to an equal dose of bimanual training in 150 infants recruited at 3-6 months. Both therapies will be parent-delivered supported by experienced clinicians. Outcomes include use of the impaired hand in bimanual tasks, cognitive and motor development at 12 and 24 months c.a. with measures of neural structure and functional connectivity at 24 months. Early interventions that attenuate
Does Antenatal Magnesium Sulphate Given To Women At Risk Of Preterm Birth Between 30 And 34 Weeks' Gestation Reduce The Risk Of Death Or Cerebral Palsy In Their Children? - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,978,760.00
Summary
Antenatal magnesium sulphate is recommended prior to preterm birth at less than 30 weeks’ gestation. Whether there are benefits at later gestations is uncertain. This study is assessing whether magnesium sulphate given to women at risk of very preterm birth between 30 to 34 weeks’ gestation increases the chance of their baby surviving without cerebral palsy.
A Pre-clinical Trial Of Early Blood Transfusion For Improving Cerebral Oxygen Delivery In Very Preterm Neonates
Funder
National Health and Medical Research Council
Funding Amount
$970,603.00
Summary
Long-term disability is common in babies born prematurely. This may be due to insufficient delivery of oxygen to the brain, but currently there is no treatment that increases oxygen delivery to the brain. We will determine if blood transfusion is more effective than current treatments given to prevent brain injury in preterm babies. Transfusion has two benefits. It will increase the amount of blood going to the brain. It will also increase the amount of oxygen carried by the blood.
Injury to the developing brain, whether sustained during pregnancy or at birth, is the underlying cause of many cognitive and motor disabilities, including cerebral palsy. This project will identify the cellular pathways that cause developmental brain injury in preterm and term infants, and then administer umbilical cord blood stem cells at different timepoints to assess their efficacy at reducing brain injury. This project will inform treatment with cord blood stem cells in high risk infants.