Cochlear Pre-Conditioning as a Modulator of Susceptibility to Hearing Loss.

SIGNIFICANCE Acquired sensorineural hearing loss is a major public health problem worldwide. The leading causes of sensorineural hearing loss are noise, aging, and ototoxic medications, with the key underlying pathology being damage to the cochlea. The review focuses on the phenomenon of pre-conditioning, in which the susceptibility to cochlear injury is reduced by exposing the ear to a stressful stimulus. Recent Advances: Cochlear conditioning has focused on the use of mono-modal conditioning, specifically conditioning the cochlea with moderate noise exposures prior to a traumatic exposure that causes permanent hearing loss. Recently, cross-modal conditioning has been explored more thoroughly, not only to prevent noise-induced hearing loss, but also age-related and drug-induced hearing losses. CRITICAL ISSUES Noise exposures that cause only temporary threshold shifts can cause long-term synaptopathy, injury to the synapses between the inner hair cells and spiral ganglion cells. This discovery has the potential to significantly alter the field of cochlear pre-conditioning with noise. Further, cochlear pre-conditioning can be the gateway to development of clinically-deployable therapeutics. Therefore, understanding the underlying mechanisms of conditioning crucial for optimizing clinical protection against sensorineural hearing loss. FUTURE DIRECTIONS Prior to the discovery of synaptopathy, noise exposures that caused only temporary threshold shifts were thought to be either harmless or potentially beneficial. Any considerations of pre-conditioning with noise must consider the potential for injury to the synapses. Further, discovery of different methods to pre-condition the cochlea against injury will yield new avenues for protection against hearing loss in the vulnerable populations.