Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has report ....Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has reported that adenosine- 5' triphosphate (ATP) causes an increase in excitatory neurotransmission from primary afferent nerves; such an increase has been reported to be painful in previous human and animal studies. Recently we have shown that the ATP induced increase in neurotransmission is dependant on activation of a specific excitatory receptor, the N-methyl D aspartate (NMDA) receptor, which has been widely implicated in other brain functions such as memory, and in disorders such as neuron death following stroke. The chief investigators involved in this application plan to study the role of the ATP receptor and the interaction with NMDA receptors in an inflammatory trigeminal pain model. Electrophysiological, pharmacological and immunohistochemical studies will be performed in order to address the aims of this proposal. A greater understanding of how these receptors modulate neurotransmission in pain pathways will lead to a greater understanding of trigeminal pain and the potential development of new therapeutics.Read moreRead less
A Wireless Electric Nerve-guide For Peripheral Nerve Repair
Funder
National Health and Medical Research Council
Funding Amount
$805,064.00
Summary
We aim to deliver a radical new precision intervention for peripheral nerve repair to improve the lives of people with peripheral nerve damage. Drawing from our recently awarded work on 'electric neural tissue engineering', we will pre-clinically test our invention of a unique clinically-amenable electric nerve-guide (e-nerve-guide), designed to act as a protective nerve conduit and wirelessly electrically-stimulate damaged nerves for their regeneration and restoration of function.
Fetomaternal Immunological Interactions In The Aetiology Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated ....There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated before birth when they are actually normal for fetal survival. In normal infants maturation of Type 1 immune responses plays a central role in switching off the Type 2 responses of fetal life. Allergic disease appears to be due to abnormal persistence of this Type 2 response pattern beyond the newborn period. One of the most striking abnormalities in allergic individuals is immature Type 1 function at birth. With rising rates of allergy, there is an urgent need to identify how the balance of Type 1 and Type 2 responses is regulated during this early period. Maternal factors appear to play a critical role. There is already evidence that Type 1 responses are lower in babies of allergic mothers compared to babies of allergic fathers, suggesting direct effects of the mother in pregnancy. Although pregnancy normally favours Type 2 immunity, there appears to be normal variation in the balance of Type 1 and Type 2 responses in pregnancy. We plan to determine if variations in this balance affect the fetal capacity for Type 1 responses. We propose that minor degrees of tissue mismatch (present in all pregnancies) will activate low grade Type 1 responses and enhance maturation of fetal Type 1 responses. We will determine if allergic mothers (prone to stronger Type 2 responses) have less developed Type 1 responses in pregnancy and if this plays a direct role in abnormal Type 1 responses observed in their babies.Read moreRead less
Axonal Regeneration And Degeneration: Cellular And Molecular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Understanding how to repair of nerve damage following a traumatic injury, a vascular accident, or a degenerative condition, is essential to develop novel effective treatments. We have identified, in a simple genetic model system, the molecular mechanisms that allow a transected nerve to be repaired by reattachment of its two separated fragments. This 'axonal fusion' process is a highly promising innovative approach that can be exploited to restore the original neuronal circuit.
Molecular And Cellular Mechanisms Of Vertebrate Brain Development
Funder
National Health and Medical Research Council
Funding Amount
$586,428.00
Summary
The essential steps in forming a normal functioning brain occur during life as an embryo. If these processes go haywire, there can be serious repercussions for life after birth. This project seeks to understand how the brain forms during embryonic stages so that better treatments and procedures can be developed to deal with developmental problems.
The Use Of Soluble Antagonists Of EphA4 In Spinal Cord Injuries
Funder
National Health and Medical Research Council
Funding Amount
$622,361.00
Summary
Permanent and limited recovery of function following spinal cord injury is a direct result of the lack of nerve regrowth through the injury. Our preliminary data suggest that antagonising the effects of EphA4, a protein involved in brain development, leads to substantial functional recovery simultaneous with nerve regrowth. In addition to designing new, more effective blockers of EphA4, we will study the signalling pathways that EphA4 activates to inhibit nerve regrowth.
Nerve growth factors are essential to promote nerve regeneration and are potential drugs for the treatment of nervous disorders such as spinal cord injury. Our recent result demonstrates that the precursor form of the nerve growth factor brain derived neurotrophic factor (proBDNF) is detrimental to an injured nervous system and can cause nerve degeneration. This project further investigates the phenomenon in order to promote treatment of spinal cord injury.
Auditory Nervous System Function After Treatment With Trophic Agents
Funder
National Health and Medical Research Council
Funding Amount
$544,890.00
Summary
Partial or complete deafness affects 11% of Australians and has great personal, social and economic cost . Worldwide, over 60,000 deaf people can now understand spoken language because of the Bionic Ear. However, after prolonged deafness, the nerves in the ear that the BIonic Ear stimulates die, reducing hearing quality. Our research tests whether biological interventions with nerve growth factors and nerve stimulation can preserve nerve function and improve hearing with the Bionic Ear.