Blast-Induced Central Auditory Neurodegeneration Affects Tinnitus Development Regardless of Peripheral Cochlear Damage.

Blast exposure causes serious complications, the most common of which are ear-related symptoms such as hearing loss and tinnitus. The blast shock waves can cause neurodegeneration of the auditory pathway in the brainstem, as well as the cochlea, which is the primary receptor for hearing, leading to blast-induced tinnitus. However, it is still unclear which lesion is more dominant in triggering tinnitus, the peripheral cochlea or the brainstem lesion owing to the complex pathophysiology and the difficulty in objectively measuring tinnitus. Recently, gap detection tests have been developed and are potentially well-suited for determining the presence of tinnitus. In this study, we investigated whether the peripheral cochlea or the central nervous system has a dominant effect on the generation of tinnitus using a blast-exposed mouse model with or without earplugs, which prevent cochlear damage from a blast transmitted via the external auditory canal. The results showed that the earplug (+) group, in which the cochlea was neither physiologically nor histologically damaged, showed a similar extent of tinnitus behavior in a gap prepulse inhibition of acoustic startle reflex test as the earplug (-) group, in which the explosion caused a cochlear synaptic loss in the inner hair cells and demyelination of auditory neurons. In contrast, both excitatory synapses labeled with VGLUT-1 and inhibitory synapses labeled with GAD65 were reduced in the ventral cochlear nucleus, and demyelination in the medial nucleus of the trapezoid body was observed in both groups. These disruptions significantly correlated with the presence of tinnitus behavior regardless of cochlear damage. These results indicate that the lesion in the brainstem could be dominant to the cochlear lesion in the development of tinnitus following blast exposure.

Low-level laser therapy for prevention of noise-induced hearing loss in rats.

Noninvasive low-level laser therapy (LLLT) is neuroprotective, but the mechanism of this effect is not fully understood. In this study, the use of LLLT as a novel treatment for noise-induced hearing loss (NIHL) is investigated. Sprague-Dawley rats were exposed to intense noise and their right ears were irradiated with an 808nm diode laser at an output power density of 110 or 165mW/cm(2) for a 30min period for 5 consecutive days. Measurement of the auditory brainstem response revealed an accelerated recovery of auditory function in the groups treated with LLLT compared with the non-treatment group at days 2, 4, 7 and 14 after noise exposure. Morphological observations also revealed a significantly higher outer hair cell survival rate in the LLLT groups. Immunohistochemical analyses for inducible nitric oxide synthase (iNOS) and cleaved caspase-3 were used to examine oxidative stress and apoptosis. Strong immunoreactivities were observed in the inner ear tissues of the non-treatment group, whereas these signals were decreased in the LLLT group at 165mW/cm(2) power density. Our findings suggest that LLLT has cytoprotective effects against NIHL via the inhibition of iNOS expression and apoptosis.

Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma.

Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.