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Abstract
Noise-induced hearing loss (NIHL) is a common injury for service members and civilians.
Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL.
There are a host of challenges in translation of investigational new drug agents from
animals into human clinical testing, however. Initial articles in this special issue
describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective
drug agents and design-related factors that impact translation of promising agents
into human clinical trials. Additional articles describe populations in which NIHL
has a high incidence and factors that affect individual vulnerability. While otoprotective
drugs will ultimately be developed for use by specific noise-exposed populations,
there has been little effort to develop pre-clinical (animal) models that accurately
model exposure hazards across diverse human populations. To facilitate advances in
the translational framework for NIHL otoprotection in pre-clinical and clinical testing,
the overarching goals of the current series are to (1) review the animal models that
have been used, highlighting the relevance to the human populations of interest, (2)
provide insight into the populations for whom pharmaceutical interventions might,
or might not, be appropriate, and (3) highlight the factors that drive the significant
individual variability observed in humans.
Common causes of hearing loss in humans - exposure to loud noise or ototoxic drugs and aging - often damage sensory hair cells, reflected as elevated thresholds on the clinical audiogram. Recent studies in animal models suggest, however, that well before this overt hearing loss can be seen, a more insidious, but likely more common, process is taking place that permanently interrupts synaptic communication between sensory inner hair cells and subsets of cochlear nerve fibers. The silencing of affected neurons alters auditory information processing, whether accompanied by threshold elevations or not, and is a likely contributor to a variety of perceptual abnormalities, including speech-in-noise difficulties, tinnitus and hyperacusis. Work described here will review structural and functional manifestations of this cochlear synaptopathy and will consider possible mechanisms underlying its appearance and progression in ears with and without traditional 'hearing loss' arising from several common causes in humans.
Exposure to intense sound or noise can result in purely temporary threshold shift (TTS), or leave a residual permanent threshold shift (PTS) along with alterations in growth functions of auditory nerve output. Recent research has revealed a number of mechanisms that contribute to noise-induced hearing loss (NIHL). The principle cause of NIHL is damage to cochlear hair cells and associated synaptopathy. Contributions to TTS include reversible damage to hair cell (HC) stereocilia or synapses, while moderate TTS reflects protective purinergic hearing adaptation. PTS represents permanent damage to or loss of HCs and synapses. While the substrates of HC damage are complex, they include the accumulation of reactive oxygen species and the active stimulation of intracellular stress pathways, leading to programmed and/or necrotic cell death. Permanent damage to cochlear neurons can also contribute to the effects of NIHL, in addition to HC damage. These mechanisms have translational potential for pharmacological intervention and provide multiple opportunities to prevent HC damage or to rescue HCs and spiral ganglion neurons that have suffered injury. This paper reviews advances in our understanding of cellular mechanisms that contribute to NIHL and their potential for therapeutic manipulation.
Background Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss, is a major health problem, is largely preventable and is probably more widespread than revealed by conventional pure tone threshold testing. Noise-induced damage to the cochlea is traditionally considered to be associated with symmetrical mild to moderate hearing loss with associated tinnitus; however, there is a significant number of patients with asymmetrical thresholds and, depending on the exposure, severe to profound hearing loss as well. Main body Recent epidemiology and animal studies have provided further insight into the pathophysiology, clinical findings, social and economic impacts of noise-induced hearing loss. Furthermore, it is recently shown that acoustic trauma is associated with vestibular dysfunction, with associated dizziness that is not always measurable with current techniques. Deliberation of the prevalence, treatment and prevention of noise-induced hearing loss is important and timely. Currently, prevention and protection are the first lines of defence, although promising protective effects are emerging from multiple different pharmaceutical agents, such as steroids, antioxidants and neurotrophins. Conclusion This review provides a comprehensive update on the pathophysiology, investigations, prevalence of asymmetry, associated symptoms, and current strategies on the prevention and treatment of noise-induced hearing loss.
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