Exposure to Intense Noise Causes Vestibular Loss.

INTRODUCTION: The vestibular system is essential for normal postural control and balance. Because of their proximity to the cochlea, the otolith organs are vulnerable to noise. We previously showed that head jerks that evoke vestibular nerve activity were no longer capable of inducing a response after noise overstimulation. The present study adds a greater range of jerk intensities to determine if the response was abolished or required more intense stimulation (threshold shift). MATERIALS AND METHODS: Vestibular short-latency evoked potential (VsEP) measurements were taken before noise exposure and compared to repeated measurements taken at specific time points for 28 days after noise exposure. Calretinin was used to identify changes in calyx-only afferents in the sacculus. RESULTS: Results showed that more intense jerk stimuli could generate a VsEP, although it was severely attenuated relative to prenoise values. When the VsEP was evaluated 4 weeks after noise exposure, partial recovery was observed. CONCLUSION: These data suggest that noise overstimulation, such as can occur in the military, could introduce an increased risk of imbalance that should be evaluated before returning a subject to situations that require normal agility and motion. Moreover, although there is recovery with time, some dysfunction persists for extended periods.

Vestibular short-latency evoked potential abolished by low-frequency noise exposure in rats.

The vestibular system plays a critical role in detection of head movements and is essential for normal postural control. Because of their anatomical proximity to the cochlea, the otolith organs are selectively exposed to sound pressure and are at risk for noise overstimulation. Clinical reports suggest a link between noise exposure and balance problems, but the structural and physiological basis for this linkage is not well understood. The goal of this study was to determine the effects of low-frequency noise (LFN) on the otolith organs by correlating changes in vestibular short-latency evoked potentials (VsEPs) with changes in saccular afferent endings following noise exposure. LFN exposure transiently abolished the VsEP and reduced the number of stained calyces within the sacculus. Although some recovery of the VsEP waveform could be observed within 3 days after noise, at 3 wk recovery was only partial in most animals, consistent with a reduced number of afferents with calyceal endings. These data show that a single intense noise exposure is capable of causing a vestibular deficit that appears to mirror the synaptic deficit associated with hidden hearing loss after noise-induced cochlear injury. NEW & NOTEWORTHY This is the first study to explore the effects of low-frequency high-intensity noise on vestibular short-latency evoked potential (VsEP) responses, which shows a linkage between attenuated noise-induced VsEPs and pathological changes to otolith organ afferents. This finding suggests a potential limitation of the VsEP for evaluation of vestibular dysfunction, since the VsEP measurement may assess the activity of a specific class rather than all afferents.

Selective hair cell ablation and noise exposure lead to different patterns of changes in the cochlea and the cochlear nucleus.

In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus (CN). However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). We showed that DT-induced HC ablation has no significant impacts on the survival of auditory neurons, central synaptic terminals, and myelin, despite complete HC loss and profound deafness. In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and CN neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination.

Nestin-expressing cells in the developing, mature and noise-exposed cochlear epithelium.

The auditory sensory epithelium in non-mammalian vertebrates can replace lost hair cells by transdifferentiation of supporting cells, but this regenerative ability is lost in the mammalian cochlea. Future cell-based treatment of hearing loss may depend on stem cell transplantation or on transdifferentiation of endogenous cells in the cochlea. For both approaches, identification of cells with stem cell features within the mature cochlea may be useful. Here we use a Nestin-ß-gal mouse to examine the presence of Nestin positive cells in the mature auditory epithelium, and determine how overstimulation of the ear impacts these cells. Nestin positive cells were found in the apical turn of the cochlea lateral to the outer hair cell area. This pattern of expression persisted into mature age. The area of Nestin positive cells was increased after the noise lesion. This increase in area coincided with an increase in expression of the Nestin mRNA. The data suggest that cells with potential stem cell features remain in the mature mammalian cochlea, restricted to the apical turn, and that an additional set of signals is necessary to trigger their contribution to cell replacement therapy in the ear. As such, this population of cells could serve to generate cochlear stem cells for research and potential therapy, and may be a target for treatments based on induced transdifferentiation of endogenous cochlear cells.

Induction of heat shock protein 32 (Hsp32) in the rat cochlea following hyperthermia.

The genes for heat shock proteins (Hsps) can be upregulated in response to cellular trauma, resulting in enhanced cell survival and protection. Hsp32, also known as heme oxygenase 1, catalyzes the degradation of heme to produce carbon monoxide and bilirubin, which play a variety of cytoprotective functions at physiological concentrations, and iron, which is rapidly sequestered by the iron-binding protein ferritin. In the present study we examined the expression and localization of Hsp32 in the rat cochlea after heat shock using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry. Low levels of constitutive Hsp32 expression were observed in the normal rat cochlea by RT-PCR and Western blot. Hsp32 mRNA (messenger RNA) was present at higher levels in a subfraction containing sensorineural epithelium and lateral wall than in a subfraction containing modiolus. Western blot revealed that Hsp32 protein levels increase in the rat cochlea following heat shock. Immunocytochemistry showed scattered staining of outer hair cells in the organ of Corti of normal untreated rats. Following heat shock Hsp32 is upregulated in outer hair cells and the cells of the stria vascularis. These results suggest a potential role for Hsp32 as a component of the oxidative stress response pathway in the rat cochlea.

Expression and localization of heat shock factor (Hsf) 1 in the rodent cochlea.

Activation of heat shock factors (Hsfs) is one of the potential mechanisms for regulating the transcription of the heat shock proteins (Hsps) and certain other stress-responsive genes. Reverse transcription polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry were used to examine the expression and localization of Hsf1, the stress-responsive member of the Hsf family, in the rat and mouse cochlea. Cerebellum was used as a positive control. Semi-quantitative RT-PCR of cochlear RNA revealed that Hsf1 was more highly expressed in a subfraction containing sensorineural epithelium and lateral wall than in a subfraction containing modiolus, with the alpha splice form predominant over the beta in both subfractions. Immunocytochemistry showed selective staining in the rodent cochlea. Hsf1 immunostaining was found in the nuclei of inner and outer hair cells in the organ of Corti, spiral ganglion cells in the modiolus, and cells in the marginal and intermediate layers of the stria vascularis. This is largely consistent with where Hsp70 induction is reported. Hsf1 activation following heat shock was examined by Western blot. Hyperthermia resulted in stress-induced Hsf1 hyperphosphorylation in cochlea as well as cerebellum. This hyperphosphorylation as well as the correlation of its localization with Hsp70 induction supports a role for Hsf1 in the cochlear stress response.