Suppression of the TGF-ß signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice.

Transforming growth factor-ß (TGF-ß) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-ß signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-ß receptor inhibitor (TGF-ßRI) onto the round window membrane. Results showed significant TGF-ß receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-ßRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-ß expression after KM-FS ototoxicity, TGF-ßRI treatment resulted in a significant decrease in TGF-ß signaling. Regarding auditory function, TGF-ßRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-ßRI treatment. These results imply that inhibition of TGF-ß signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.

Research Application of Laser-induced Shock Wave for Studying Blast-induced Cochlear Injury.

The ear is the organ most susceptible to explosion overpressure, and cochlear injuries frequently occur after blast exposure. Blast exposure can lead to sensorineural hearing loss (SNHL), which is an irreversible hearing loss that negatively affects the quality of life. Detailed blast-induced cochlear pathologies, such as the loss of hair cells, spiral ganglion neurons, cochlear synapses, and disruption of stereocilia, have been previously documented. However, determining cochlear sensorineural deterioration after a blast injury is challenging because animals exposed to blast overpressure usually experience tympanic membrane perforation (TMP), which causes concurrent conductive hearing loss. To evaluate pure sensorineural cochlear dysfunction, we developed an experimental animal model of blast-induced cochlear injury using a laser-induced shock wave. This method avoids TMP and concomitant systemic injuries and reproduces the functional decline in the SNHL component in an energy-dependent manner after LISW exposure. This animal model could be a platform for elucidating the pathological mechanisms and exploring potential treatments for blast-induced cochlear dysfunction.

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.

Effect of statins on hearing outcome in patients with idiopathic sudden sensorineural hearing loss.

Objective: Statins have been reported to improve vascular endothelial function and microcirculation, reduce oxidative stress, and exert anti-inflammatory and protective effects against inner ear damage. Therefore, this study aimed to investigate the effect of statins on hearing prognosis in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: We reviewed the medical records of 149 patients diagnosed with ISSNHL. Clinical characteristics, hearing thresholds, statin medications, and hematological findings were investigated. First, patients with ISSNHL were assigned to the good and poor outcome groups, and factors influencing their prognosis were analyzed. Furthermore, patients with dyslipidemia were investigated to determine whether statins have therapeutic effects on ISSNHL. Results: Significant differences in age (p = .011), days from the onset of ISSNHL to the initiation of treatment (p = .04), and hematological total cholesterol (TC; p = .015) between the good and poor outcome groups were observed. Furthermore, when hearing outcomes were investigated in patients with dyslipidemia, TC was significantly lower in the good outcome group (p = .03). Although no significant therapeutic effects of statins were observed in participants with dyslipidemia, patients in the statin-treated group were significantly older and experienced more diabetic complications than those in the non-statin-treated group. Conclusion: Although our study showed that dyslipidemia is a poor prognostic factor for ISSNHL, statins had no significant therapeutic effects on hearing recovery in ISSNHL patients with dyslipidemia. The patients that received statin medications were significantly older and experienced more diabetic complications, which may have affected their hearing prognosis. Level of Evidence: Level 4.

Is repetitive systemic corticosteroid therapy effective for idiopathic sudden sensorineural hearing loss? a retrospective study.

Introduction: Some idiopathic sudden sensorineural hearing loss (ISSHL) cases experience repetitive systemic corticosteroid treatment, but studies focusing on repetitive systemic corticosteroid administration have not been reported. Thus, we investigated the clinical characteristics and usefulness of repetitive systemic corticosteroid treatment in ISSHL cases. Methods: We reviewed the medical records of 103 patients who received corticosteroids only in our hospital (single-treatment group), and 46 patients who presented at our hospital after receiving corticosteroids in a nearby clinic and were subsequently treated with corticosteroids again in our hospital (repetitive-treatment group). Clinical backgrounds, hearing thresholds, and hearing prognosis were assessed. Results: The final hearing outcomes were not different between the two groups. Further, in the repetitive-treatment group, statistical differences were found between the good and poor prognosis groups in the number of days to start corticosteroid administration (p = 0.03), the dose of corticosteroid (p = 0.02), and the duration of corticosteroid administration (p = 0.02) at the previous facility. Multivariate analysis revealed a significant difference in the dose of corticosteroids administered by the previous clinic (p = 0.004). Conclusion: The repetitive systemic corticosteroid administration might play a supplementary role in hearing improvement, and initial sufficient corticosteroid administration would lead to good hearing outcomes in an early phase of ISSHL.

Investigation of hearing aid fitting according to the national acoustic laboratories' prescription for non-linear hearing aids and the desired sensation level methods in Japanese speakers: a crossover-controlled trial.

OBJECTIVE: Some studies have directly compared the National Acoustic Laboratories' prescription for non-linear hearing aids (HAs) version 2 (NAL-NL2) and Desired Sensation Level for non-linear HAs version 5 (DSLv5), although none were performed in Japan. As the Japanese language is a tonal language that has different linguistic characteristics than those of the studied languages, we compared the outcomes of the NAL-NL2 and DSLv5 in hearing-impaired Japanese participants. METHODS: A crossover-controlled trial was conducted on 18 first-time HA users with bilateral moderate sensorineural hearing loss. Participants wore HAs adjusted with each prescriptive method for four weeks. The prescriptions were assessed using speech discrimination testing and the abbreviated profile of hearing aid benefit (APHAB). Consequently, participants were asked to select their preferred prescription and determine which was better for "listening to a conversation" and when "noisy." RESULTS: The mean DSLv5 real ear insertion gain for an input level of 65 dB sound pressure level (SPL) was higher than that of the NAL-NL2 at 250 and 500 Hz. The average speech discrimination score was 78 ± 14% at a 65-dB SPL and 75 ± 17% at an 80-dB SPL for the NAL-NL2, and 79 ± 11% at a 65-dB SPL and 77 ± 17% at an 80-dB SPL for the DSLv5. These differences were not significant. No significant differences were observed in APHAB subscale scores between the two prescription methods. Ultimately, 11 (61%) and 7 (39%) participants preferred the NAL-NL2 and DSLv5, respectively, with no significant differences. CONCLUSION: Although the gain of the NAL-NL2 is smaller than that of the DSLv5, both had the same hearing effect. Therefore, the NAL-NL2 may be more useful than the DSLv5 in Japanese.

Effects of Unilateral Vagotomy on LPS-Induced Aspiration Pneumonia in Mice.

Respiratory-related dysphagia and aspiration pneumonia can be attributed to multiple causes. However, reproduction of multiple factor-related respiratory distress and aspiration pneumonia in a single animal model is challenging. To validate animals with vagal nerve palsy as novel models for severe aspiration pneumonia associated with respiratory distress, we investigated the effects of unilateral vagotomy on the swallowing function and severity of pneumonia after forced aspiration in mice. Unilateral vagotomy was performed in C57BL6 male mice that subsequently underwent evaluation of swallowing function by videofluoroscopic swallow study (VFSS) and histological assessments for aspiration pneumonia induced by lipopolysaccharide (LPS). VFSS examinations demonstrated that unilateral vagotomy did not cause apparent aspiration in mice, but it resulted in a significant loss of body weight (BW) due to decreased oral intake. In addition, when aspiration pneumonia was induced by forced administration of LPS, significantly prolonged BW loss and severe infiltration of inflammatory cells associated with aspiration pneumonia were observed in the mice that underwent unilateral vagotomy. In conclusion, the vagotomized mice showed appropriate characteristics as a model of aspiration pneumonia caused by multiple factors, including the paralysis of vocal fold movement and respiratory distress. This model can help elucidate the pathogenesis of aspiration pneumonia and the treatment methods for the respiration-compromised model.

Clinical Characteristics and Corticosteroid Responses of Acoustic Neuroma Treated as Idiopathic Sudden Sensorineural Hearing Loss.

BACKGROUND: Few investigations have been conducted on the clinical characteristics of the differential diagnosis of acoustic neuroma with acute sensorineural hearing loss and idiopathic sudden sensorineural hearing loss. The aim of the study was to investigate the clinical characteristics of the differential diagnoses between acoustic neuroma and idiopathic sudden sensorineural hearing loss. METHODS: The medical records of patients with acute sensorineural hearing loss (142 ears), including acoustic neuroma (19 ears) and idiopathic sudden sensorineural hearing loss (123 ears), who underwent audiometric and hematologic examinations and received systemic corticosteroid treatment, were retrospectively reviewed. RESULTS: Hematological examination revealed that the erythrocyte sedimentation rate and fibrinogen values were significantly higher in the idiopathic sudden sensorineural hearing loss group compared to the acoustic neuroma group. Although all patients received corticosteroid treatment, hearing thresholds at the initial examination and 3 months after corticosteroid treatment were significantly higher in the idiopathic sudden sensorineural hearing loss group compared to the acoustic neuroma group at all frequencies. However, hearing recovery was worse in the acoustic neuroma group compared to the idiopathic sudden sensorineural hearing loss group. Furthermore, speech discrimination and short increment sensitivity index tests were not significantly different between the acoustic neuroma and idiopathic sudden sensorineural hearing loss groups. CONCLUSION: This is the first study to reveal that speech discrimination and short increment sensitivity index tests are not useful for the differential diagnoses between acoustic neuroma and idiopathic sudden sensorineural hearing loss, whereas erythrocyte sedimentation rate and fibrinogen, blood biomarkers of inflammation and blood viscosity, would be considered valuable. Furthermore, acoustic neuroma should be considered in cases where acute sensorineural hearing loss did not recover after corticosteroid treatment, although the initial hearing loss was mild.

Factors affecting the incidence of chorda tympani nerve transection in middle ear surgery.

Objective: To reveal the factors affecting the incidence of chorda tympani nerve (CTN) transection during middle ear surgery. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: We analyzed 232 ears (117 ears with cholesteatoma, 101 ears with chronic otitis media, and 14 ears with otosclerosis) that underwent tympanoplasty or stapes surgery during 2017-2020. Intervention: Eighty-four ears underwent transcanal endoscopic ear surgery (TEES), 103 ears underwent microscopic ear surgery (MES), and 45 ears underwent surgery using both endoscopy and microscopy (Dual). Main Outcome Measure: To confirm CTN transection, intraoperative endoscopic/microscopic video images were evaluated. We used the same video images to determine the anatomical variation of the CTN course in the middle ear. Results: In 18 ears (7.8%: 6/84 TEES ears [7.1%], 6/103 MES ears [5.8%], and 6/45 Dual ears [13.3%]), the CTN was cut during middle ear surgery. There was no significant difference in CTN transection among groups. In cholesteatoma patients, stapes involvement resulted in a significantly higher CTN transection incidence. CTN anatomical variants such as the "Attached Short type" and "Ultrashort type" showed a significantly higher CTN transection incidence. Conclusion: Although endoscopic surgery did not reduce the incidence of CTN transection during middle ear surgery, pathological involvement of the stapes and CTN anatomical variants, such as the "Attached Short type" and "Ultrashort type," may increase this incidence. Preoperative evaluation of stapes involvement and anatomical location of the CTN course could help identify patients at greater risk for iatrogenic CTN transection. Level of Evidence: 4.

Immune-Nutritional Status as a Novel Prognostic Predictor of Bell's Palsy.

INTRODUCTION: The prognosis of Bell's palsy, idiopathic facial nerve palsy (FNP), is usually predicted by electroneuronography in subacute phase. However, it would be ideal to establish a reliable and objective examination applicable in acute phase to predict the prognosis of FNP. Immune-nutritional status (INS) calculated from peripheral blood examination is recently reported as the prognostic factor in various disease. However, the validity of INS as the prognostic factor in Bell's palsy is not well known. Thus, we conducted a retrospective study to investigate the usefulness of INS as prognostic predictors of Bell's palsy. METHODS: We reviewed the medical records of 79 patients with Bell's palsy and divided into two groups as "complete recovery" and "incomplete recovery" groups. Clinical features such as severity of FNP and INS, including neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutrition status (CONUT) score, were assessed. RESULTS: In univariate analysis, statistically significant differences were observed in clinical score of facial movement, NLR, LMR, PNI, and CONUT score at the initial examination between the two groups (p < 0.05). Furthermore, in multivariate analysis, statistically significant differences were also observed in facial movement score and PNI at the initial examination (p < 0.05). CONCLUSION: Immune and nutritional condition play important roles in the pathogenesis of Bell's palsy, suggesting that INS would be one of the useful prognostic factors in Bell's palsy.

Correlation of Blast-Induced Tympanic Membrane Perforation with Peripheral Cochlear Synaptopathy.

The auditory organs, including the tympanic membrane, cochlea, and central auditory pathway, are the most fragile components of the human body when exposed to blast overpressure. Tympanic membrane perforation (TMP) is the most frequent symptom in blast-exposed patients. The impact of TMP on the inner ear and central auditory system, however, is not fully understood. We aimed to analyze the effect of blast-induced TMP on the auditory pathophysiological changes in mice after blast exposure. Mice aged seven weeks were exposed to blast overpressure to induce TMP and allowed to survive for two months. All TMP cases had spontaneously healed by week three after the blast exposure. Compared with controls, blast-exposed mice exhibited a significant elevation in hearing thresholds and an apparent disruption of stereocilia in the outer hair cells, regardless of the occurrence or absence of TMP. The reduction in synapses in the inner hair cells, which is known as the most frequent pathology in blast-exposed cochleae, was significantly more severe in mice without TMP. A decrease in the number of excitatory central synapses labeled by VGLUT-1 in the cochlear nucleus was observed, however, regardless of the absence or presence of TMP. Our findings suggest that blast-induced TMP mitigates peripheral cochlear synaptic disruption but leaves the central auditory synapses unaffected, indicating that central synaptic disruption is independent of TMP and peripheral cochlear synaptic disruption. Synaptic deterioration in the peripheral and central auditory systems can contribute to the promotion of blast-induced hearing impairment, including abnormal auditory perception.

Clinical features and hearing prognosis of idiopathic sudden sensorineural hearing loss in patients undergoing hemodialysis: A retrospective study.

BACKGROUND: Patients undergoing hemodialysis (HD) tend to experience hearing loss, including idiopathic sudden sensorineural hearing loss (ISSHL). However, little is known about the relationship between HD and ISSHL. OBJECTIVE: To investigate the effects of HD on the hearing level and the treatment prognosis of ISSHL. METHODS: We reviewed the medical records of 23 patients with ISSHL receiving HD treatment (HD group) and 101 patients with ISSHL not receiving HD treatment (non-HD group), and assessed clinical features, results of audiometric tests and blood examination results. RESULTS: Statistically significant differences were not observed in pretreatment hearing level and hearing recovery of the ear affected with ISSHL between the two groups (P > .05). Conversely, hearing thresholds in the unaffected ear were statistically different (P < .0001), and the hearing thresholds of the HD groups were significantly increased compared with those of the non-HD groups, especially at high frequency. In addition, patients with renal dysfunction not receiving HD treatment showed similar hearing thresholds in the unaffected ear when compared with patients receiving HD treatment. CONCLUSION: HD itself did not influence the treatment prognosis of ISSHL. Renal dysfunction itself, and not HD treatment, worsened the hearing level. As similar treatment results are expected, standard treatment should be administered to patients undergoing HD. LEVEL OF EVIDENCE: 3b.

Inhibition of extracellular signal-regulated kinase pathway suppresses tracheal stenosis in a novel mouse model.

Tracheal stenosis is a refractory and recurrent disease induced by excessive cell proliferation within the restricted tracheal space. We investigated the role of extracellular signal-regulated kinase (ERK), which mediates a broad range of intracellular signal transduction processes in tracheal stenosis and the therapeutic effect of the MEK inhibitor which is the upstream kinase of ERK. We histologically analyzed cauterized tracheas to evaluate stenosis using a tracheal stenosis mouse model. Using Western blot, we analyzed the phosphorylation rate of ERK1/2 after cauterization with or without MEK inhibitor. MEK inhibitor was intraperitoneally injected 30 min prior to cauterization (single treatment) or 30 min prior to and 24, 48, 72, and 96 hours after cauterization (daily treatment). We compared the stenosis of non-inhibitor treatment, single treatment, and daily treatment group. We successfully established a novel mouse model of tracheal stenosis. The cauterized trachea increased the rate of stenosis compared with the normal control trachea. The phosphorylation rate of ERK1 and ERK2 was significantly increased at 5 min after the cauterization compared with the normal controls. After 5 min, the rates decreased over time. The daily treatment group had suppressed stenosis compared with the non-inhibitor treatment group. p-ERK1/2 activation after cauterization could play an important role in the tracheal wound healing process. Consecutive inhibition of ERK phosphorylation is a potentially useful therapeutic strategy for tracheal stenosis.

Effect of shock wave power spectrum on the inner ear pathophysiology in blast-induced hearing loss.

Blast exposure can induce various types of hearing impairment, including permanent hearing loss, tinnitus, and hyperacusis. Herein, we conducted a detailed investigation of the cochlear pathophysiology in blast-induced hearing loss in mice using two blasts with different characteristics: a low-frequency dominant blast generated by a shock tube and a high-frequency dominant shock wave generated by laser irradiation (laser-induced shock wave). The pattern of sensorineural hearing loss (SNHL) was low-frequency- and high-frequency-dominant in response to the low- and high-frequency blasts, respectively. Pathological examination revealed that cochlear synaptopathy was the most frequent cochlear pathology after blast exposure, which involved synapse loss in the inner hair cells without hair cell loss, depending on the power spectrum of the blast. This pathological change completely reflected the physiological analysis of wave I amplitude using auditory brainstem responses. Stereociliary bundle disruption in the outer hair cells was also dependent on the blast's power spectrum. Therefore, we demonstrated that the dominant frequency of the blast power spectrum was the principal factor determining the region of cochlear damage. We believe that the presenting models would be valuable both in blast research and the investigation of various types of hearing loss whose pathogenesis involves cochlear synaptopathy.

Decreasing auditory input induces neurogenesis impairment in the hippocampus.

Hearing loss is associated with cognitive decline and dementia risk. Sensorineural hearing loss suppresses hippocampal neurogenesis, resulting in cognitive decline. However, the underlying mechanism of impaired neurogenesis and the role of microglial activation and stress responses related to hearing loss in the hippocampus remains unknown. Using a conductive hearing loss (CHL) model, we investigated whether a decrease in sound level could induce impairment of hippocampal neurogenesis and examined the differences between unilateral CHL (uCHL) and bilateral CHL (bCHL). To establish the CHL mouse model, ears were unilaterally or bilaterally occluded for five weeks by auditory canal ligation. Although hearing thresholds were significantly increased following CHL, CHL mice exhibited no significant loss of spiral ganglion or hippocampal neurons. Hippocampal neurogenesis was significantly and equally decreased in both sides following uCHL. More severe decreases in hippocampal neurogenesis were observed in both sides in bCHL mice compared with that in uCHL mice. Furthermore, microglial invasion significantly increased following CHL. Serum cortisol levels, which indicate stress response, significantly increased following bCHL. Therefore, auditory deprivation could lead to increased microglial invasion and stress responses and might be a risk factor for hippocampal neurogenesis impairment.

Speech discrimination impairment of the worse-hearing ear in asymmetric hearing loss.

OBJECTIVE: This study aimed to compare the difference in maximum speech discrimination score (SDSmax) of the worse-hearing ear in asymmetric hearing loss (ASHL) patients with that in symmetric hearing loss (SHL) patients. DESIGN: We retrospectively reviewed medical records of patients with suspected hearing loss (HL) who underwent audiometric examinations. Patients were divided into two groups according to the difference in air conduction (AC) threshold between the right and left ears: the SHL group and the ASHL group. STUDY SAMPLE: Of the 102 patients (204 ears), 74 (148 ears) had SHL, and 28 had ASHL. RESULTS: The worse-hearing ear of ASHL patients exhibited a statistically significantly higher AC threshold and lower SDSmax, compared with ears of SHL patients and better-hearing ears of ASHL patients, and SDSmax exhibited a statistically significant negative correlation with AC threshold. The SDSmax was statistically significantly lower in the worse-hearing ear of the ASHL group than in moderate to severe HL ears of the SHL group, even though these groups had comparable AC thresholds. CONCLUSIONS: ASHL patients' worse-hearing ear exhibited a lower SDSmax than SHL patients' ears, despite a comparable AC threshold. Management of hearing impairment in ASHL patients should receive more attention.

Activity-Dependent Neurodegeneration and Neuroplasticity of Auditory Neurons Following Conductive Hearing Loss in Adult Mice.

We examined the functional and structural changes of auditory neurons (ANs) in adult mice after conductive hearing loss (CHL). Earplugs (EPs) were bilaterally inserted in male 8-week-old mice for 4 weeks [EP(+) group] and subsequently removed for 4 weeks [EP(+/-) group]. We examined the control mice [EP(-) group] with no EPs inserted at 12 weeks. The auditory brainstem response (ABR) was measured to determine the cochlear function before and after EP insertion, after EP removal, and at 4 weeks following EP removal. We examined the cochleae for hair cell (HC) and spiral ganglion neuron survival, synaptic and neural properties, and AN myelination. There was a significant elevation of the ABR threshold across all tested frequencies after EP insertion. After removing the occlusion, these threshold shifts were fully recovered. Compared with the EP(-) mice, the EP(+) mice showed a significant decrease in the ABR peak 1 amplitude and a significantly prolonged latency at all tested frequencies. There was no significant effect of auditory deprivation on the survival of HCs and ANs. Conversely, auditory deprivation caused significant damage to the synapses and myelin and a significant decrease in the AN size. Although functional changes in the ABR amplitude and latency did not fully recover in the EP(+/-) mice, almost all anatomical changes were fully recovered in the EP(+/-) mice; however, cochlear synapses only showed partial recovery. These results suggest that auditory activities are required to maintain peripheral auditory synapses and myelination in adults. The auditory deprivation model allows for assessment of the mechanisms of synaptopathy and demyelination in the auditory periphery, and synaptic and myelin regeneration in sensorineural hearing loss.

Scar Formation and Debris Elimination during Hair Cell Degeneration in the Adult DTR Mouse.

The auditory sensory epithelium of the mammalian inner ear is a highly organized structure that contains sensory hair cells (HCs) and non-sensory supporting cells (SCs). Following the partial loss of HCs after cochlear insults such as overstimulation or ototoxic drugs, SCs seal the luminal epithelial surface (reticular lamina) and reorganize its cellular pattern. Here we investigated the changes in the sensory epithelium following a rapid and severe cochlear insult in the diphtheria toxin receptor (DTR) mouse, where diphtheria toxin (DT) injection leads to a HC-specific lesion resulting in a complete HC loss. We found that DT-induced selective HC ablation could lead to a pattern of scar formation and apical cell-cell adherens and tight junction reorganization similar to that occurring after other types of cochlear insult. Prestin, an outer HC-specific protein, was present in amorphous clumps at the sites where SCs had expanded to fill the spaces vacated by the dead HCs for up to 2 months after the DT induced lesion. Many of the prestin clumps appeared to occupy spaces within SCs, suggesting that SCs participate in the removal process of HC corpses in the DTR deafness model. Prestin clumps could be seen in different areas all along the length of the SCs, and appeared to be inside the SCs as well as in the inter-cellular spaces between SCs. The findings suggest that HC elimination in the DTR deafness model follows a mechanism similar to that in overstimulation or ototoxicity models, making the DTR mouse useful for understanding the process underlying HC elimination and the role of SCs in this process.

Comparison of real-ear insertion gains in Japanese-speaking individuals wearing hearing aids with DSLv5 and NAL-NL2.

OBJECTIVE: We used real-ear insertion gain (REIG), with the international speech test signal (ISTS), to evaluate the amplifying characteristics of hearing aids, set for patients who have been wearing such aids for a long time in a stable manner. We further compared this to the target values of the DSLv5 and NAL-NL2 methods. METHODS: The subjects were adults with moderate sensorineural hearing loss. We examined 40 ears in 25 individuals (15 people wearing hearing aids in both ears and ten people wearing aid in only one ear). Fit assessments were performed based on the speech performance-intensity functions and tolerance of environmental noise, and the ears studied were categorized as either ears with sufficient benefit or ears with insufficient benefit. Additionally, we evaluated the REIG for international speech test signals at 65-dB and 80-dB sound pressure level (SPL). We compared the REIG and target values for voice input at 65-dB and 80-dB SPL, calculated from the DSLv5 and NAL-NL2 methods. RESULTS: Among the 40 ears, 34 received sufficient benefit and six received an insufficient benefit from hearing aids. The REIG for ISTS at 65-dB in the sufficient benefit ears, at frequencies of 1,000 Hz and 2,000 Hz, were similar to the target values of NAL-NL2 and DSLv5 but were significantly lower at 250 Hz, 500 Hz, and 4,000 Hz frequencies. The compression ratio of REIG for sufficient benefit ears was similar to that of DSLv5. The REIG for ISTS at 65-dB in the insufficient benefit ears was smaller than that in the sufficient benefit ears at frequencies of 2,000 Hz and 4,000 Hz. CONCLUSION: This study suggested that the target values of NAL-NL2 and DSLv5 are appropriate, even for Japanese-speaking individuals, at mid-pitch sounds. Although it is necessary to investigate the necessity for low-pitch and high-pitch gains further in the future, this study provides meaningful data regarding the amplifying characteristics in Japanese-speaking individuals who have been wearing hearing aids in a stable manner.

Long-term administration of vitamin B12 and adenosine triphosphate for idiopathic sudden sensorineural hearing loss: a retrospective study.

BACKGROUND: In idiopathic sudden sensorineural hearing loss (ISSNHL), the relationship between the administration duration of vitamin B12 (vit B12) with adenosine triphosphate (ATP) and their therapeutic effect is not fully understood. OBJECTIVE: To investigate the therapeutic effect of long-term 16 (≥weeks) administration of vit B12 with ATP on the prognosis of ISSNHL patients and compare it with those of short-term (<8 weeks) and middle-term (≥8 weeks, <16 weeks) administration. METHODS: We retrospectively reviewed the medical records of 117 patients with ISSNHL treated between 2015 and 2018. RESULTS: The overall recovery rate was 32.5%. Initial higher hearing threshold and initial higher grade of hearing loss (HL) were associated with a poor prognosis. However, the administration duration of vit B12 and ATP did not influence the overall hearing improvement. With regard to the time course of hearing recovery, there was no significant difference in hearing recovery among the long-, middle-, and short-term administration groups until 16 weeks after treatment. However, at 16-24 weeks after initial treatment, the short-term administration group exhibited significantly lower hearing recovery than did the long-term administration groups. CONCLUSIONS: The administration duration of vit B12 and ATP did not influence the overall hearing prognosis in ISSNHL, but long-term administration of vit B12 and ATP helped prevent the progression of HL after ISSNHL. Our results suggest that long-term administration of vit B12 and ATP is not necessarily required to treat ISSNHL patients, except for slowly progressing HL in the affected ears.