NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less
Hearing Protection Conferred By P2X2 Receptor Signaling In The Cochlea
Funder
National Health and Medical Research Council
Funding Amount
$580,019.00
Summary
Hearing loss from noise damage and ageing is the principal sensory disability in our society. This project will determine the contribution of the P2X2 receptor to protection from noise-induced hearing loss. We have found that P2X2 knockout mice have minimal temporary threshold shift. We will investigate the physiological basis for this and determine why this mouse model has greater hearing loss with intense sound and faster age-related hearing loss compared with wildtype controls.
Improving Music Appreciation For People With Prosthetic Hearing Devices By Enhancing Auditory Stream Segregation
Funder
National Health and Medical Research Council
Funding Amount
$266,560.00
Summary
Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people wi ....Music perception is one of the most often-cited problems for people with hearing aids or cochlear implants. Part of the problem is related to the reduced ability to hear different instruments or melodic lines separately. This ability is based on perceptual differences between auditory streams. Psychophysics experiments will be performed to understand the effect of different acoustic parameters on auditory streaming. An innovative approach to restore music appreciation will be tested on people with impaired hearing.Read moreRead less
Lung infections are the most frequent triggers of asthma exacerbations. While different infections cause exacerbations by they all result in the same type of lung inflammation. Using novel disease models, we have identified key molecules involved in a range of viral and bacterial induced asthma exacerbations. We will define these shared pathways that link viral and bacterial-mediated asthma exacerbations, thus these studies will pave the way for the development of unified treatments.
Web Based Study Of Risk Factors For Pain Exacerbation In Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$408,501.00
Summary
While much is known about the risk factors for radiographic knee OA, the risk factors for symptoms emanating from joints affected by OA remain unclear. Identifying modifiable methods for alleviating pain and or avoiding risk factors for exacerbations of pain could have tremendous public health importance. In the proposed study we will use the Internet to facilitate data collection to test a set of risk factors for knee pain fluctuation among subjects with symptomatic radiographic knee OA.
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
FETAL BRAIN INJURY RESULTING FROM INTRAUTERINE INFECTION: LONG TERM CONSEQUENCES AND THE POTENTIAL FOR INTERVENTION
Funder
National Health and Medical Research Council
Funding Amount
$452,640.00
Summary
Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. Unfortunately, at present, it is not possible to prevent or effectively treat brain damage in the fetu ....Brain damage during fetal life is a significant cause of later neurological problems such as cerebral palsy. Recent studies have shown that brain injury detected in infants is usually caused by adverse conditions within the uterus prior to labour, but the exact causes are poorly understood. It is also apparent that babies born prematurely are at increased risk of suffering serious brain damage. Unfortunately, at present, it is not possible to prevent or effectively treat brain damage in the fetus or newborn, partly due to ignorance about how and when the damage is occurring. In recent years it has become evident that infections in the mother, may be linked to both premature birth and brain damage. It has been proposed that the certain chemicals (cytokines) which are released during an infection can across the placenta to the fetus, causing inflammatory changes that lead to brain damage. However, although associations have been shown in studies of women, there is little evidence that infections actually cause brain damage in the fetus. This project will define the effects of an inflammation inducing chemical (bacterial endotoxin) on the fetal brain and the pattern of inflammation it sets up in the fetus. We will also examine the effects of brain damage caused by endotoxin in the newborn lamb, and relate this to alterations in behaviour. Once we have defined the effects of endotoxin on brain structure, we will test the effects of chemicals that are known to block the actions of inflammatory cytokines. We hope that by blocking the chemical pathway that leads to the production of harmful cytokines we may be able to prevent brain injury from occurring when the fetus is exposed to an infection in the mother. It is expected that this project will provide important information that helps us to understand how infection in the mother can cause brain injury in the fetus. This information is vital if strategies to prevent or treat brain injury are to be developed.Read moreRead less
Role Of Toll-like Receptor 7 In Rhinovirus-induced Asthma Exacerbation
Funder
National Health and Medical Research Council
Funding Amount
$697,248.00
Summary
One third of the annual asthma-related health care expenditure may be attributable to asthma-related hospitalisations. Even mild asthmatics experience severe exacerbations at a rate of almost one per year1 and those attacks can be fatal. Rhinovirus (RV) causes the majority of asthma exacerbations which may be linked to an impaired antiviral interferon (IFN) response in asthmatics. RV is sensed by Toll-like receptor (TLR) 7, but the role of this innate host defence pathway in regulating antiviral