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This document is an editorial published in the journal Frontiers in Integrative Neuroscience. The editorial focuses on bilateral vestibulopathy (BVP), a condition characterized by imbalance, unsteady gait, oscillopsia, and bilateral loss of vestibular function. The editorial highlights recent advances in understanding BVP, including diagnostic criteria, environmental factors that may contribute to the condition, and the impact of BVP on mobility and cognitive function. The editorial also discusses the importance of questionnaires and neuroimaging in diagnosing and monitoring BVP, as well as the potential role of cumulative noise exposure in the development of the condition. Additionally, the editorial explores the impact of BVP on hearing, canal and otolith organ function, and walking ability. The authors hope that readers will find value in the integration of recent studies on BVP and related topics. [Extracted from the article]

Introduction: The vestibular system integrates signals related to vision, head position, gravity, motion, and body position to provide stability during motion through the environment. Disruption in any of these systems can reduce agility and lead to changes in ability to safely navigate one's environment. Causes of vestibular decline are diverse; however, excessive noise exposure can lead to otolith organ dysfunction. Specifically, 120 decibel (dB) sound pressure level (SPL) 1.5 kHz-centered 3-octave band noise (1.5 kHz 3OBN) causes peripheral vestibular dysfunction in rats, measured by vestibular short-latency evoked potential (VsEP) and reduced calretinin-immunolabeling of calyx-only afferent terminals in the striolar region of the saccule. The present study examined the functional impact of this noise exposure condition, examining changes in motor performance after noise exposure with a balance beam crossing task. Methods: Balance beam crossing time in rats was assessed for 19 weeks before and 5 weeks after noise exposure. Balance beam crossings were scored to assess proficiency in the task. When animals were proficient, they received a single exposure to 120 dB SPL 3-octave band noise. Results: During the initial training phase slower crossing times and higher scores, including multiple failures were observed. This was followed by a period of significant improvement leading to proficiency, characterized by fast and stable crossing times and consistently low scores. After noise exposure, crossing times were significantly elevated from baseline for 4-weeks. A total of 5 weeks after noise exposure, crossing times improved, and though still trending higher than baseline, they were no longer significantly different from baseline. Discussion: These findings show that the noise-induced peripheral vestibular changes we previously observed at cellular and electro-physiological levels also have an impact at a functional level. It has been previously shown that imbalance is associated with slower walking speed in older adults and aged rats. These findings in noise-exposed rats may have implications for people who experience noisy environments and for seniors with a history of noise exposure who also experience balance disorders and may be at increased fall risk. [ABSTRACT FROM AUTHOR]

Exposure to 120 dB sound pressure level (SPL) band-limited noise results in delayed onset latency and reduced vestibular shortlatency evoked potential (VsEP) responses. These changes are still present 4 wk after noise overstimulation. Noise-induced hearing loss (NIHL) has been shown to vary in extent and duration based on the noise intensity. This study investigated whether noise-induced peripheral vestibular hypofunction (NPVH) would also decrease in extent and/or duration with less intense noise exposure. In the present study, rats were exposed to a less intense noise (110 dB SPL) but for the same duration (6 h) and frequency range (500–4,000 Hz) as used in previous studies. The VsEP was assessed 1, 3, 7, 14, 21, and 28 days after noise exposure. In contrast to 120 dB SPL noise exposure, the 110 dB SPL noise exposures produced smaller deficits in VsEP responses that fully recovered in 62% (13/21) of animals within 1 wk. These findings suggest that NPVH, a loss or attenuation of VsEP responses with a requirement for elevated stimulus intensity to elicit measurable responses, is similar to NIHL, that is, lower sound levels produce a smaller or transient deficit. These results show that it will be important to determine the extent and duration of vestibular hypofunction for different noise exposure conditions and their impact on balance. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half of the cochlea at 22 months of age compared to mice without rapamycin. The present study tested adding rapamycin to diet later in life, at 14 months of age, and added a longitudinal assessment of auditory brain stem response (ABR). The present study used UMHET4 mice, a 4 way cross in which all grandparental strains lack the Cdh23753A allele that predisposes to early onset, progressive hearing loss. UMHET4 mice typically have normal hearing until 16–17 months, then exhibit threshold shifts at low frequencies/apical cochlea and later in more basal high frequency regions. ABR thresholds at 4, 12, 24, and 48 kHz were assessed at 12, 18, and 24 months of age and compared to baseline ABR thresholds acquired at 5 months of age to determine threshold shifts (TS). There was no TS at 12 months of age at any frequency tested. At 18 months of age mice with rapamycin added to diet at 14 months had a significantly lower mean TS at 4 and 12 kHz compared to mice on control diet with no significant difference at 24 and 48 kHz. At 24 months of age, the mean 4 kHz TS in rapamycin diet group was no longer significantly lower than the control diet group, while the 12 kHz mean remained significantly lower. Mean TS at 24 and 48 kHz in the rapamycin diet group became significantly lower than in the control diet group at 24 months. Hair cell counts at 24 months showed large loss in the apical half of most rapamycin and control diet mice cochleae with no significant difference between groups. There was only mild outer hair cell loss in the basal half of rapamycin and control diet mice cochleae with no significant difference between groups. The results show that a later life addition of rapamycin can decrease age-related hearing loss in the mouse model, however, it also suggests that this decrease is a delay/deceleration rather than a complete prevention. [ABSTRACT FROM AUTHOR]

Despite our understanding of the impact of noise-induced damage to the auditory system, much less is known about the impact of noise exposure on the vestibular system. In this article, we review the anatomical, physiological, and functional evidence for noise-induced damage to peripheral and central vestibular structures. Morphological studies in several animal models have demonstrated cellular damage throughout the peripheral vestibular system and particularly in the otolith organs; however, there is a paucity of data on the effect of noise exposure on human vestibular end organs. Physiological studies have corroborated morphological studies by demonstrating disruption across vestibular pathways with otolith-mediated pathways impacted more than semicircular canal-mediated pathways. Similar to the temporary threshold shifts observed in the auditory system, physiological studies in animals have suggested a capacity for recovery following noise-induced vestibular damage. Human studies have demonstrated that diminished sacculo-collic responses are related to the severity of noise-induced hearing loss, and dose-dependent vestibular deficits following noise exposure have been corroborated in animal models. Further work is needed to better understand the physiological and functional consequences of noise-induced vestibular impairment in animals and humans. [ABSTRACT FROM AUTHOR]

A major challenge for those studying noise-induced injury pre-clinically is the selection of an animal model. Noise injury models are particularly relevant in an age when people are constantly bombarded by loud noise due to occupation and/or recreation. The rat has been widely used for noise-related morphological, physiological, biochemical, and molecular assessment. Noise exposure resulting in a temporary (TTS) or permanent threshold shift (PTS) yields trauma in peripheral and central auditory related pathways. While the precise nature of noise-related injuries continues to be delineated, both PTS and TTS (with or without hidden hearing loss) result in homeostatic changes implicated in conditions such as tinnitus and hyperacusis. Compared to mice, rats generally tolerate exposure to loud sounds reasonably well, often without exhibiting other physical non-inner ear related symptoms such as death, loss of consciousness, or seizures [Skradski, Clark, Jiang, White, Fu, and Ptacek (2001). Neuron 31, 537–544; Faingold (2002). Hear. Res. 168, 223–237; Firstova, Abaimov, Surina, Poletaeva, Fedotova, and Kovalev (2012). Bull Exp. Biol. Med. 154, 196–198; De Sarro, Russo, Citraro, and Meldrum (2017). Epilepsy Behav. 71, 165–173]. This ability of the rat to thrive following noise exposure permits study of long-term effects. Like the mouse, the rat also offers a well-characterized genome allowing genetic manipulations (i.e., knock-out, viral-based gene expression modulation, and optogenetics). Rat models of noise-related injury also provide valuable information for understanding mechanistic changes to identify therapeutic targets for treatment. This article provides a framework for selection of the rat as a model for noise injury studies. [ABSTRACT FROM AUTHOR]

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 shortlatency 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. [ABSTRACT FROM AUTHOR]

Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post-implantation hearing outcomes, it requires protection from implant insertion-induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide-co-glycolide (PLGA), and one composed of acetal-modified dextran and PLGA. Following in vivo infusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post-infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post-infusion compared to pre-infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil-loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post-infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1510-1522, 2016. [ABSTRACT FROM AUTHOR]

SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2(Δ/Δ)resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven(N7) (99 % FVB). Slc44a2(Δ/Δ) mice produced abnormally spliced Slc44a2 transcripts that contain a frame shift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2(Δ/Δ) mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age,Slc44a2(Δ/Δ) mice exhibited hearing loss at 32 kHz,but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2(+/+) and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2(Δ/Δ) mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2(Δ) mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2(Δ/Δ) mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing. [ABSTRACT FROM AUTHOR]

Diverse cellular and environmental stresses can activate the heat shock response, an evolutionarily conserved mechanism to protect proteins from denaturation. Stressors activate heat shock transcription factor 1 (HSF1), which binds to heat shock elements in the genes for heat shock proteins, leading to rapid induction of these important molecular chaperones. Both heat and noise stress are known to activate the heat shock response in the cochlea and protect it from subsequent noise trauma. However, the contribution of HSF1 to induction of heat shock proteins following noise trauma has not been investigated at the molecular level. We evaluated the role of HSF1 in the cochlea following noise stress by examining induction of heat shock proteins in Hsf1 control and Hsf1 mice. Heat stress rapidly induced expression of Hsp25, Hsp47, Hsp70.1, Hsp70.3, Hsp84, Hsp86, and Hsp110 in the cochleae of wild-type and Hsf1 mice, but not in Hsf1 mice, confirming the essential role of HSF1 in mediating the heat shock response. Exposure to broadband noise (2-20 kHz) at 106 dB SPL for 2 h produced partial hearing loss. Maximal induction of heat shock proteins occurred 4 h after the noise. In comparison to heat stress, noise stress resulted in lower induced levels of Hsp25, Hsp70.1, Hsp70.3, Hsp86, and Hsp110 in Hsf1 mice. Induction of these heat shock proteins was attenuated, but not completely eliminated, in Hsf1 mice. These same noise exposure conditions induced genes for several immediate early transcription factors and maximum induction occurred earlier than for heat shock proteins. Thus, additional signaling pathways and transcriptional regulators that are activated by noise probably contribute to induction of heat shock proteins in the cochlea. [ABSTRACT FROM AUTHOR]

Diverse cellular and environmental stresses can activate the heat shock response, an evolutionarily conserved mechanism to protect proteins from denaturation. Stressors activate heat shock transcription factor 1 (HSF1), which binds to heat shock elements in the genes for heat shock proteins, leading to rapid induction of these important molecular chaperones. Both heat and noise stress are known to activate the heat shock response in the cochlea and protect it from subsequent noise trauma. However, the contribution of HSF1 to induction of heat shock proteins following noise trauma has not been investigated at the molecular level. We evaluated the role of HSF1 in the cochlea following noise stress by examining induction of heat shock proteins in Hsf1 ( +/- ) control and Hsf1 ( -/- ) mice. Heat stress rapidly induced expression of Hsp25, Hsp47, Hsp70.1, Hsp70.3, Hsp84, Hsp86, and Hsp110 in the cochleae of wild-type and Hsf1 ( +/- ) mice, but not in Hsf1 ( -/- ) mice, confirming the essential role of HSF1 in mediating the heat shock response. Exposure to broadband noise (2-20 kHz) at 106 dB SPL for 2 h produced partial hearing loss. Maximal induction of heat shock proteins occurred 4 h after the noise. In comparison to heat stress, noise stress resulted in lower induced levels of Hsp25, Hsp70.1, Hsp70.3, Hsp86, and Hsp110 in Hsf1 ( +/- ) mice. Induction of these heat shock proteins was attenuated, but not completely eliminated, in Hsf1 ( -/- ) mice. These same noise exposure conditions induced genes for several immediate early transcription factors and maximum induction occurred earlier than for heat shock proteins. Thus, additional signaling pathways and transcriptional regulators that are activated by noise probably contribute to induction of heat shock proteins in the cochlea. [ABSTRACT FROM AUTHOR]

A mouse embry- onic stem (ES) cell line containing an inducible transgene for the proneural gene Neurogi has been used to generate glutamatergic neurons at a high efficiency. The present study used in vitro electro- physiology to establish the timeline for acquiring a functional neuro- nal phenotype in Neurog]-induced cells exhibiting a neuronal mor- phology. TTX-sensitive action potentials could be evoked from over 80% of the cells after only 4.5 days in vitro (Dlv). These cells uniformly showed rapidly adapting responses to current injection, firing one to three action potentials at the onset of the stimulus. In the absence of Neurog], a limited number of ES cells adopted a neuronal morphology, but these cells displayed slow calcium depolarizations rather than sodium-based spikes. Voltage-gated Na+, K+, and Ca2+ currents were present in nearly all induced cells as early as 4.5 DIV. The voltage-dependent properties of these currents changed little from 4 to 12 DIV with half-activation voltage varying by <10 mV for any current type throughout the culture period. This study demonstrates that forced expression of proneural genes can induce ES cells to quickly acquire a functional neuronal phenotype with mature electro- physiological properties. Transient overexpression of Neurogi may be used in neural repair strategies that require the rapid induction of functional neurons from pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate the ototoxic potential of ciprofloxacin hydrochloride, 0.3%, plus dexamethasone, 0.1%, after administration to the guinea pig middle ear. Design: Fifty guinea pigs were randomly assigned to 4 test groups of 10 animals each and 2 control groups of 5 animals each. The 4 test groups were treated twice daily for 4 weeks with 10 μL of (1) ciprofloxacin hydrochloride, 0.3%, plus dexamethasone, 0.1%; (2) ciprofloxacin hydrochloride, 1.0%, plus dexamethasone, 0.3%; (3) ciprofloxacin hydrochloride, 0.3%, or (4) vehicle. The positive and negative control groups were treated with neomycin sulfate, 10%, or isotonic sodium chloride solution, respectively. Setting: Academic research laboratory. Interventions: Study animals were implanted with a drug delivery cannula to the middle ear, terminating in the round window niche for direct delivery to the round window membrane. Main Outcome Measures: Auditory brainstem responses were collected at baseline and following 2 and 4 weeks of dosing. At the termination of the study, inner ear tissues were evaluated microscopically. Results: No biologically relevant hearing losses were observed after either 2 or 4 weeks of treatment with vehicle, ciprofloxacin alone, or combinations of ciprofloxacin plus dexamethasone. Examination of the organ of Corti revealed normal hair cell counts in all animals that received isotonic sodium chloride solution, vehicle, ciprofloxacin, or combinations of ciprofloxacin and dexamethasone. Conversely, the neomycin sulfate positive control group demonstrated a significant elevation in hearing threshold and profound hair cell loss (P<.001, P =.02, and P<001 at 2, 8, and 16 kHz, respectively). Conclusion: The results of this preclinical study support the safety of ciprofloxacin hydrochloride, 0.3%, plus dexamethasone, 0.1%, for clinical use in the open middle ear cavity. [ABSTRACT FROM AUTHOR]

Differentiation of the pluripotent neuroepithelium into neurons and glia is accomplished by the interaction of growth factors and cell-type restricted transcription factors. One approach to obtaining a particular neuronal phenotype is by recapitulating the expression of these factors in embryonic stem (ES) cells. Toward the eventual goal of auditory nerve replacement, the aim of the current investigation was to generate auditory nerve-like glutamatergic neurons from ES cells. Transient expression of Neurog1 promoted widespread neuronal differentiation in vitro; when supplemented with brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), 75% of ES cell-derived neurons attained a glutamatergic phenotype after 5 d in vitro. Mouse ES cells were also placed into deafened guinea pig cochleae and Neurog1 expression was induced for 48 h followed by 26 d of BDNF/GDNF infusion. In vivo differentiation resulted in 50-75% of ES cells bearing markers of early neurons, and a majority of these cells had a glutamatergic phenotype. This is the first study to report a high percentage of ES cell differentiation into a glutamatergic phenotype and sets the stage for cell replacement of auditory nerve. [ABSTRACT FROM AUTHOR]

The inferior colliculus (IC) is a major center of integration in the ascending as well as descending auditory pathways, where both excitatory and inhibitory amino acid neurotransmitters play a key role. When normal input to the auditory system is decreased, the balance between excitation and inhibition in the IC is disturbed. We examined global changes in gene expression in the rat IC 3 and 21 days following bilateral deafening, using Affymetrix GeneChip arrays and focused our analysis on changes in expression of neurotransmission-related genes. Over 1400 probe sets in the Affymetrix Rat Genome U34A Array were identified as genes that were differentially expressed. These genes encoded proteins previously reported to change as a consequence of deafness, such as calbindin, as well as proteins not previously reported to be modulated by deafness, such as clathrin. A subset of 19 differentially expressed genes was further examined using quantitative RT–PCR at 3, 21 and 90 days following deafness. These included several GABA, glycine, glutamate receptor and neuropeptide-related genes. Expression of genes for GABA-A receptor subunitsβ2,β3, andγ2, plus ionotropic glutamate receptor subunits AMPA 2, AMPA 3, and kainate 2, increased at all three times. Expression of glycine receptor α1 initially declined and then later increased, whileα2 increased sharply at 21 days. Glycine receptorα3 increased between 3 and 21 days, but decreased at 90 days. Of the neuropeptide-related genes tested with qRT–PCR, tyrosine hydroxylase decreased approximately 50% at all times tested. Serotonin receptor 2C increased at 3, 21, and 90 days. The 5B serotonin receptor decreased at 3 and 21 days and returned to normal by 90 days. Of the genes tested with qRT–PCR, only glycine receptorα2 and serotonin receptor 5B returned to normal levels of expression at 90 days. Changes in GABA receptorβ3, GABA receptor γ2, glutamate receptor 2/3, enkephalin, and tyrosine hydroxylase were further confirmed using immunocytochemistry. [ABSTRACT FROM AUTHOR]

Investigates whether neutotrophic factor (NTF) intervention restores auditory function in deafened animals. Ability of NTF to enhance threshold sensitivity within the auditory system; Survival of auditory spiral ganglion neurons.

High-throughput DNA microarray technology allows for the assessment of large numbers of genes and can reveal gene expression in a specific region, differential gene expression between regions, as well as changes in gene expression under changing experimental conditions or with a particular disease. The present study used a gene array to profile normal gene expression in the rat whole cochlea, two subregions of the cochlea (modiolar and sensorineural epithelium), and the cochlear nucleus and inferior colliculus of the auditory brainstem. The hippocampus was also assessed as a well-characterized reference tissue. Approximately 40% of the 588 genes on the array showed expression over background. When the criterion for a signal threshold was set conservatively at twice background, the number of genes above the signal threshold ranged from approximately 20% in the cochlea to 30% in the inferior colliculus. While much of the gene expression pattern was expected based on the literature, gene profiles also revealed expression of genes that had not been reported previously. Many genes were expressed in all regions while others were differentially expressed (defined as greater than a twofold difference in expression between regions). A greater number of differentially expressed genes were found when comparing peripheral (cochlear) and central nervous system regions than when comparing the central auditory regions and the hippocampus. Several families of insulin-like growth factor binding proteins, matrix metalloproteinases, and tissue inhibitor of metalloproteinases were among the genes expressed at much higher levels in the cochlea compared with the central nervous system regions. [ABSTRACT FROM AUTHOR]

The transient expression of stress proteins in cells exposed to adverse environmental conditions is thought to provide a survival advantage. In the present study, the expression of the major mammalian stress protein, Hsp72, was characterized in the rat peripheral auditory system following varying periods of unilateral cochlear ischemia and reperfusion. Western blot analysis of whole cochlear homogenates revealed Hsp72 expression after as little as 5 minutes of cochlear ischemia. Cochlear Hsp72 immunoreactivity following 10 minutes of ischemia was observed within 2 hours, remained evident through 6 hours, and decreased toward control levels by 12 hours. Preliminary immunocytochemical localization data revealed Hsp72 expression in the outer hair cells. The characterization of Hsp72 expression following transient ischemia represents the first step toward understanding the role that stress proteins have in the protection of the mammalian auditory system. [ABSTRACT FROM AUTHOR]

The presence of immune-mediated hearing loss was investigated in an animal model. Eight guinea pigs and four mice underwent immunizations with a preparation of chick or guinea pig cochlear tissue and Freund's adjuvant. Hearing thresholds were monitored by auditory brainstem response (ABR) testing over a 5-week period after immunization. The serum and temporal bones of test and control animals were then examined using an enzyme-linked im-munosorbent assay (ELISA), immunocytochemical, and his-tological techniques. Hearing loss of 20 dB or greater occurred in eight animals. ELISA demonstrated antibodies to cochlear antigens in the sera of all test animals. Immunocytochemistry revealed immunostaining of hair cell stereocilia in the organ of Corti and saccule. Endolymphatic hydrops, and organ of Corti degeneration was observed in the temporal bones of three animals. This study provides evidence to suggest that cross-species immunization with cochlear antigens might produce a humoral response that can be associeted with inner ear pathologic change and sensorineural hearing lose. [ABSTRACT FROM AUTHOR]

The cochlear prosthesis is not applicable to patients who lack an implantable cochlea or an intact vestibulocochlear nerve. Direct electrical stimulation of the cochlear nucleus (CN) of the brain stem might provide a method for auditory rehabilitation of these patients. A penetrating CN electrode has been developed and tissue tolerance to this device demonstrated. This study was undertaken to evaluate metabolic activation of central nervous system (CNS) auditory tracts produced by such implants. Regional cerebral glucose use resulting from CN stimulation was estimated in a series of chronically implanted guinea pigs with the use of [14C]−2-deoxyglucose (2-DG). Enhanced 2-DG uptake was observed in structures of the auditory tract. The activation of central auditory structures achieved with CN stimulation was similar to that produced by acoustic stimulation and by electrical stimulation of the modiolar portion of the auditory nerve in control groups. An interesting banding pattern was observed in the inferior colliculus following CN stimulation, as previously described with acoustic stimulation. This study demonstrates that functional metabolic activation of central auditory pathways can be achieved with a penetrating CNS auditory prosthesis. [ABSTRACT FROM AUTHOR]