Voltage Dependent Calcium Channels And Vascular Function: Do Microdomains Determine Function?
Funder
National Health and Medical Research Council
Funding Amount
$597,682.00
Summary
Blood flow depends on arterial diameter which can change with contraction of muscle in the vessel wall. Calcium influx through one type of channel in the muscle cells has been considered critical, but drugs targeting these channels have not succeeded in treating the arterial spasm which occurs after stroke and head injury. Our study will investigate the existence and role of other calcium channels in brain arteries. Knowledge gained will likely lead to development of new drug targets for stroke.
Establishing A Model Of Occlusive Middle Cerebral Artery Stroke In The Sheep
Funder
National Health and Medical Research Council
Funding Amount
$74,365.00
Summary
Stroke is the second leading cause of death and the highest cause of disability in adult Australians, however our lack of an animal model that correctly replicates the human condition has severely hindered our understanding and treatment of the disease. This research project aims to develop a model of stroke in the sheep using a surgical approach that future researchers may use and adapt to further explore the physiology of the disease and trial therapeutic techniques to treat stroke.
A Novel Ionic Current Contributing To Spasm Of Small Blood Vessels
Funder
National Health and Medical Research Council
Funding Amount
$287,500.00
Summary
Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a n ....Vascular smooth muscle can produce strong constrictions or spasms that can severely limit blood flow. Disorders arising from such spasms include sudden death, neurological deficits, visual and hearing loss or impairment, Raynaud's phenomenon (painful episodic contraction of the fingers and toes) and intestinal necrosis. Common mechanisms are likely to underlie the spasms associated with these disparate disorders. In a recent electrophysiological study of vascular smooth muscle, we discovered a novel membrane current which we refer to as the plateau current. This current has a strong depolarizing influence that is likely to make a major contribution to the spasms, particularly in arterioles and small arteries which are more dependent on depolarization for contraction. Block of this current is expected to minimize the depolarization and therefore prevent or ameliorate spasm of the vessels. Thus the plateau current represents a new field of therapeutic potential for addressing vascular problems that have significant health implications. However, therapeutic manipulation of the current requires knowledge of its properties. In this project we will determine the biophysical and pharmacological properties of this current using voltage-clamp techniques. We will then use this information to assess its functional significance by recording membrane potential with intracellular microelectrodes simultaneously with contractile activity. We will also compare small vessels obtained from volunteers with or without the vasospastic disorder of Raynaud's phenomenon. Our previous work using these techniques was described in J Physiol as a microelectrode, patch clamp and myograph study of the highest quality and of supreme technical difficulty and scored a Top-Ten hit rate. Since we are the only ones to record the plateau current, we are in a unique position to make significant progress to our understanding of contraction, including spasm, in small blood vessels.Read moreRead less
Early Identification Of Infants Who Will Benefit From Neural Rescue Treatment
Funder
National Health and Medical Research Council
Funding Amount
$206,320.00
Summary
Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the exte ....Lack of oxygen supply before, during or immediately after birth can lead to severe disability or death. This occurs in about 1 in every 500 births and is one of the most important but unsolved problems in pediatrics. The costs (financial and other) to both the individuals involved, and the community in general, is very high. However the outlook for those affected by this condition is improving. Recent research has focused on the development of neural rescue therapies, which may decrease the extent of disabilities suffered by these children. The same treatments may also be helpful in children following near drowning and head trauma. Neural rescue therapies must be applied less than 24 hours following the event which has caused the reduction in oxygen supply. Thus, before these treatments can be tested, it is necessary to find a way to quickly tell which babies may benefit from the treatments. This study will trial a new method which is inexpensive and can be used without moving the baby away from its incubator. This technique involves a new application of an established technology to detect the redistribution of water within the brain one of the earliest signs of impending brain cell death. The research team consists of medical personnel from the intensive care nurseries of both the Royal Women's Hospital and the Mater Mother s Hospital, as well as scientific staff experienced in the use of this technology. If this technique is effective, it will enable babies to receive maximum benefit from new treatments and reduce long-term difficulties suffered by these children and their families.Read moreRead less
COMBIT: Randomised Controlled Trial Of Novel Upper Neurorehabilitation For Congenital Hemiplegia
Funder
National Health and Medical Research Council
Funding Amount
$486,588.00
Summary
Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of t ....Cerebral palsy is the most common disability in children - there are over one million children with the hemiplegic form in the industrialised world. Rehabilitation to improve hand use impacts on daily care, access to education and vocational aspirations, and consumes a great deal of time and money. Our team wishes to test a novel COMbined Constraint and BImanual Training study (COMBIT) in a randomized controlled trial investigating upper limb function, participation and mechanisms of action of the intervention.Read moreRead less
Training To Enhance Lower Limb Motor Control In Hemiplegic Cerebral Palsy.
Funder
National Health and Medical Research Council
Funding Amount
$107,204.00
Summary
Currently very few evidence based methods that can improve control in muscles affected by cerebral palsy (CP) exist. This project will investigate whether it is possible to increase strength and co-ordination in legs muscles affected by CP through targeted training. The project will also determine if non-invasive brain stimulation during training may enhance motor learning and if positive gains in strength and co-ordination might enhance the ability to do tasks like walking or climbing stairs.
Implementing Neuroprotective Strategies For Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$782,370.00
Summary
Fetal growth restriction (FGR) is a serious and common complication of pregnancy that is a principal cause of injury to the developing fetal brain. In turn, damage to the developing brain during pregnancy may cause cerebral palsy and other cognitive and behavioural deficits. This proposal builds on my work to date characterising the mechanisms that contribute to neuropathology in FGR infants, by implementing targeted strategies to protect or repair the FGR brain.
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.