Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. To investigate expression and function of Tmc1 and Tmc2 in vestibular organs, we used quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization - hairpin chain reaction (FISH-HCR), immunostaining, FM1-43 uptake and we measured vestibular evoked potentials (VsEPs) and vestibular ocular reflexes (VORs). We found that Tmc1 and Tmc2 showed dynamic developmental changes, differences in regional expression patterns, and overall expression levels which differed between the utricle and saccule. These underlying changes contributed to unanticipated phenotypic loss of VsEPs and VORs in Tmc1 KO mice. In contrast, Tmc2 KO mice retained VsEPs despite the loss of the calcium buffering protein calretinin, a characteristic biomarker of mature striolar calyx-only afferents. Lastly, we found that neonatal Tmc1 gene replacement therapy is sufficient to restore VsEP in Tmc1 KO mice for up to six months post-injection.

Nestin expression is associated with pluripotency. Growing evidence suggests nestin is involved in hair cell development. The objective of this study was to investigate the morphology and role of nestin-expressing cells residing in the early postnatal murine inner ear. A lineage-tracing nestin reporter mouse line was used to further characterize these cells. Their cochleae and vestibular organs were immunostained and whole-mounted for cell counting. We found Nestin-expressing cells present in low numbers throughout the inner ear. Three morphotypes were observed: bipolar, unipolar, and globular. Mitotic activity was noted in nestin-expressing cells in the cochlea, utricle, saccule, and crista. Nestin-expressing cell characteristics were then observed after hair cell ablation in two mouse models. First, a reporter model demonstrated nestin expression in a significantly higher proportion of hair cells after hair cell ablation than in control cochleae. However, in a lineage tracing nestin reporter mouse, none of the new hair cells which repopulated the organ of Corti after hair cell ablation expressed nestin, nor did the nestin-expressing cells change in morphotype. In conclusion, Nestin-expressing cells were identified in the cochlea and vestibular organs. After hair cell ablation, nestin-expressing cells did not react to the insult. However, a small number of nestin-expressing cells in all inner ear tissues exhibited mitotic activity, supporting progenitor cell potential, though perhaps not involved in hair cell regeneration.

The biochemistry of diabetes mellitus results in multi-system tissue compromise that reduces functional mobility and interferes with disease management. Sensory system compromise, such as peripheral neuropathy and retinopathy, are specific examples of tissue compromise detrimental to functional mobility. There is lack of clarity regarding if, when, and where parallel changes in the peripheral vestibular system, an additional essential sensory system for functional mobility, occur as a result of diabetes. Given the systemic nature of diabetes and the plasticity of the vestibular system, there is even less clarity regarding if potential vestibular system changes impact functional mobility in a meaningful fashion. This commentary will provide insight as to when we should employ diagnostic vestibular function tests in people with diabetes, where in the periphery we should look, and why testing may or may not matter. The commentary concludes with recommendations for future research and clinical care.

UNASSIGNED: Cervical vestibular evoked myogenic potentials (cVEMPs) provide an objective measure of the integrity of the sacculo-collic pathway leading to their widespread use as a clinical tool in the diagnostic vestibular test battery. Though the application of cVEMPs in preclinical models to assess vestibular function, as performed in relevant clinical populations, remains limited. The present study aimed to establish a rodent model of cVEMP with standardized methods and protocols, examine the neural basis of the responses, and characterize and validate important features for interpretation and assessment of vestibular function.
UNASSIGNED: We compared air-conducted sound (ACS)-evoked VEMPs from the sternocleidomastoid muscles in naïve Brown Norway rats. A custom setup facilitated repeatable and reliable measurements which were carried out at multiple intensities with ACS between 1 and 16 kHz and over 7 days. The myogenic potentials were identified by the presence of a positive (P1)-negative (N1) waveform at 3-5 ms from the stimulus onset. Threshold, amplitude, and latency were compared with intensity- and frequency-matched responses within and between animals.
UNASSIGNED: cVEMP responses were repeatedly evoked with stimulus intensities between 50-100 dB SPL with excellent test-retest reliability and across multiple measurements over 7 days for all frequencies tested. Suprathreshold, cVEMP responses at 90 dB SPL for 6-10 kHz stimuli demonstrated significantly larger amplitudes (p < 0.01) and shorter latencies (p < 0.001) compared to cVEMP responses for 1-4 kHz stimuli. Latency of cVEMP showed sex-dependent variability, but no significant differences in threshold or amplitude between males and females was observed.
UNASSIGNED: The results provide a replicable and reliable setup, test protocol, and comprehensive characterization of cVEMP responses in a preclinical model which can be used in future studies to elucidate pathophysiological characteristics of vestibular dysfunctions or test efficacy of therapeutics.

BACKGROUND: The aqeductus vestibuli (aqueduct) is believed to connect to the saccule in embryos and adults. However, in embryos, the saccule and utricle are known to communicate widely to provide a common endolymph space \"atrium\".
METHODS: Using sagittal histological sections from five embryos (crown-rump length or CRL, 14-21 mm), nine early fetuses (CRL 24-35 mm) and 12 midterm and near-term fetuses (CRL 82-272 mm), we revisited the development and growth of the human ear aqueduct.
RESULTS: The atrium took on a thick tube-like appearance as an antero-inferior continuation of the aqueduct, but soon divided into multiple gulfs. Most of the gulfs corresponded to the ampullae of semicircular ducts, while one gulf at the antero-medio-inferior corner corresponded to the future saccule. Notably, in eight of the 14 embryos and early fetuses, the aqueduct ended at the utricle near the primitive ampulla of the anterior (superior) or posterior semicircular duct. Conversely, an embryo of CRL 21 mm was the smallest specimen in which the aqueduct joined the gulf-like saccule. At midterm and near-term, the growing perilymph space separated the aqueduct from the utricle and appeared to push the aqueduct toward the saccule. A topographical change occurred between the embryonic superiorly located utricle and the inferiorly-located saccule to create the antero-posterior arrangement in adults.
CONCLUSIONS: Consequently, the vestibular end of the aqueduct was most likely to migrate anteriorly from the utricle to the saccule at 6-8 weeks possibly due to differential growth of the endothelium. Previous reconstructions of the embryonic aqueduct might be biased by the adult morphology.

Cochlear implantation surgery (CI) is considered a safe procedure and is the standard treatment for the auditory rehabilitation in patients with severe-to-profound sensorineural hearing loss. Although the development of minimally traumatic surgical concepts (MTSC) have enabled the preservation of residual hearing after the implantation, there is scarce literature regarding the vestibular affection following MTCS. The aim of the study is to analyze histopathologic changes in the vestibule after CI in an animal model (Macaca fascicularis). Cochlear implantation was performed successfully in 14 ears following MTCS. They were classified in two groups upon type of electrode array used. Group A (n = 6) with a FLEX 28 electrode array and Group B (n = 8) with HL14 array. A 6-month follow-up was carried out with periodic objective auditory testing. After their sacrifice, histological processing and subsequent analysis was carried out. Intracochlear findings, vestibular presence of fibrosis, obliteration or collapse is analyzed. Saccule and utricle dimensions and neuroepithelium width is measured. Cochlear implantation was performed successfully in all 14 ears through a round window approach. Mean angle of insertion was >270° for group A and 180-270° for group B. In group A auditory deterioration was observed in Mf 1A, Mf2A and Mf5A with histopathological signs of scala tympani ossification, saccule collapse (Mf1A and Mf2A) and cochlear aqueduct obliteration (Mf5A). Besides, signs of endolymphatic sinus dilatation was seen for Mf2B and Mf5A. Regarding group B, no auditory deterioration was observed. Histopathological signs of endolymphatic sinus dilatation were seen in Mf 2B and Mf 8B. In conclusion, the risk of histological damage of the vestibular organs following minimally traumatic surgical concepts and the soft surgery principles is very low. CI surgery is a safe procedure and it can be done preserving the vestibular structures.

The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse frequency- or pulse amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone.NEW & NOTEWORTHY Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.

The gold standard for diagnosis of laryngeal paralysis is laryngoscopy under light anesthesia. This prospective analytical cross-sectional study aimed to determine whether a radiographic assessment of the larynx could be used as a non-invasive screening tool for diagnosing laryngeal paralysis in non-sedated animals, as the laryngeal ventricles may appear wider in affected animals. The laryngeal ventricles of 18 dogs with bilateral laryngeal paralysis composing the affected group and 25 non-sedated dogs presenting no respiratory abnormality composing the control group were evaluated using right lateral radiography of the larynx. Three observers measured the ratios of the maximal ventricular length and surface to the body length of the third cervical vertebra (MVL/LC3 and VS/LC3, respectively). They also subjectively assessed the ventricular shape as either normal or rounded. The most accurate criterion was found to be MVL/LC3, as the respective areas under the ROC curves were 0.96 (95% confidence interval [CI]: 0.95-0.97), 0.89 (95% CI: 0.87-0.91), 0.80 (95% CI: 0.65-0.95) for MVL/LC3, VS/LC3, and ventricular shape evaluation, respectively. Based on ROC curve analysis, two thresholds of clinical interest were set for the MVL/LC3; bilateral laryngeal paralysis was very unlikely for values < 0.3 and very likely for values > 0.5. The findings of this study support the use of lateral laryngeal radiography as a screening tool for diagnosing bilateral laryngeal paralysis. However, further diagnostic tests remain required if MVL/LC3 lies between these threshold values or if clinically indicated. Further studies are warranted to explore the use of laryngeal radiography in unilateral paralysis and other laryngeal or oropharyngeal diseases.

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UNASSIGNED: This study aims to investigate the potential vestibular pathway impairment through vestibular evoked myogenic potentials (VEMPs) and to explore the pathophysiological significance of these instrument-based findings in children with recurrent vertigo.
UNASSIGNED: The clinical data of 21 children (mean age 4.67 ± 1.39 years) diagnosed as RVC who met the inclusion criteria of the Bárány Society and 29 healthy children (mean age 4.83 ± 1.34 years) enrolled as the control group from February 2021 to December 2021 were collected and analyzed retrospectively. All the subjects underwent both cervical VEMP (cVEMP) and ocular VEMP (oVEMP) triggered by air-conducted sound (ACS) and galvanic vestibular stimulation (GVS), respectively. The elicit rate, latency, and amplitude asymmetry ratio (AAR) of ACS-cVEMP, ACS-oVEMP, GVS-cVEMP, and GVS-oVEMP were analyzed.
UNASSIGNED: (1) The elicit rates of ACS-cVEMP and ACS-oVEMP were similar in the two groups (P > 0.05), as well as GVS-cVEMP and GVS-oVEMP (P > 0.05). (2) P1 and N1 latencies of ACS-cVEMP and GVS-cVEMP in the RVC group were longer than those in the control group (P < 0.05). (3) The N1 latency of ACS-oVEMP in the RVC group was shorter than that in the control group (P < 0.05), while there was no significant difference in the P1 latency of ACS-oVEMP (P > 0.05). The N1 and P1 latencies of GVS-oVEMP were not significantly different (P > 0.05). (4) There was no statistical difference in the AAR of ACS-cVEMP and GVS-cVEMP. Although there was an increased AAR of ACS-oVEMP in the RVC group (P < 0.05), the AAR was within the normal range. However, no statistical difference was found in the AAR of GVS-oVEMP in the two groups (P > 0.05).
UNASSIGNED: The latencies of ACS-cVEMP and GVS-cVEMP in children with recurrent vertigo were significantly prolonged compared with those in healthy children, and there was no difference in elicit rates of ACS-cVEMP and GVS-cVEMP, suggesting that there might be potential impairment in the inferior vestibular nerve and the subsequent nerve conduction pathway in RVC.