Hearing Research最新文献

{"title":"Acoustic masking of electric stimulation at basal and extra-cochlear sites.","authors":"Patrick Hinz, Waldo Nogueira","doi":"10.1016/j.heares.2026.109835","DOIUrl":"https://doi.org/10.1016/j.heares.2026.109835","url":null,"abstract":"<p><p>Cochlear implant (CI) candidates with residual low-frequency hearing increasingly receive hearing-preserving electrode arrays to enable electric-acoustic stimulation (EAS). However, assessing very low-frequency hearing in newborns and young children remains difficult. Previous work has shown that acoustic stimulation can mask electrically evoked auditory percepts when stimulation sites are spatially separated. Whether such masking also occurs when electric stimulation is delivered near the round window (RW), prior to cochlear insertion, remains unclear. This study investigated ipsilateral acoustic masking of electric stimulation delivered at apical, basal, and near-RW sites in 12 EAS users with residual low-frequency hearing implanted with short or partially inserted electrode arrays. Using a psychophysical paradigm, threshold elevations of electric pulse trains were measured during simultaneous acoustic stimulation. Electric stimulation was applied at extra-cochlear RW locations and intra-cochlear basal and apical electrodes, while stimulation parameters were systematically varied. With Individually optimized parameters, electric stimulation near the RW reliably evoked auditory percepts without side effects in 8 of 12 participants, though optimal stimulation parameters and masking strength varied across participants. Strong acoustic masking was consistently observed for apical stimulation, whereas weaker but measurable masking occurred for basal and RW stimulation. A cochlear lumped-parameter model indicated that approximately 5% of current delivered at the RW can reach apical regions, explaining the observed masking by low-frequency acoustic tones. Masking strength correlated with residual hearing for apical stimulation only. These findings indicate that acoustic masking of apical electric stimulation, which correlated with residual hearing, holds potential as a diagnostic tool for assessing low-frequency hearing post-operatively. The detection of masking during both RW and basal stimulation represents a promising result, indicating that these stimulation paradigms can produce quantifiable effects. Given the considerable variability observed among participants, further investigation is required to establish the extent to which masking measures reflect residual hearing or hearing loss. Nonetheless, these results provide novel insight into auditory perception and side effects associated with basal and extra-cochlear electric stimulation, informing future efforts to optimize this approach for low-frequency hearing assessment.</p>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"483 ","pages":"109835"},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149266280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship of sound transmission and ossicular chain mobility: investigations for the development of an intraoperative predictive surgical tool using a robotic approach","authors":"Christoph Müller,&nbsp;Nico Bilic,&nbsp;Matthias Bornitz,&nbsp;Marcus Neudert,&nbsp;Thomas Zahnert,&nbsp;Martin Koch","doi":"10.1016/j.heares.2025.109509","DOIUrl":"10.1016/j.heares.2025.109509","url":null,"abstract":"<div><div>Intraoperative assessment of ossicular chain mobility remains challenging in reconstructive middle-ear surgery because conventional palpation is subjective. To better predict the postoperative air–bone gap (ABG) and guide decisions on whether revision surgery may be beneficial for hearing restoration, a more refined intraoperative assessment that differentiates the degree of ossicular chain mobility reduction is required. In this ex vivo study, we evaluated whether quasi-static stiffness measurements can predict sound transmission.</div><div>Twelve human cadaveric temporal bones were mounted on a robotic setup in which a force-sensing needle robotically executed a standardized palpation sequence along a predefined trajectory, enabling calculation of direction-specific stiffness metrics. Stepwise artificial stiffening of the annular ligament, the stapes superstructure and the surrounding anatomical spaces of the tympanic cavity with thin layers of UV-curable resin produced graded sound transmission losses across up to five increments (for a total of ≈20–30 dB). The derived stiffness metrics tracked this decline only partially and anisotropically, with changes corresponding to &lt;10 dB equivalents in specific probing directions. Nevertheless, binomial generalized linear models identified stiffness thresholds that discriminated among clinically relevant ABG categories (&lt;10 dB, 10–20 dB, &gt;20 dB). Similar trends were observed in three additional specimens with an opened incudostapedial joint. These finding demonstrate that quantitative force measurements or simplified surgical tools fitted to specific force thresholds could potentially provide surgeons with an intraoperative evaluation support tool.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109509"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian control of the peripheral vestibular organs in rodents and humans","authors":"Evangelia Tserga ,&nbsp;Ivan A. Lopez ,&nbsp;Barbara Canlon","doi":"10.1016/j.heares.2026.109572","DOIUrl":"10.1016/j.heares.2026.109572","url":null,"abstract":"<div><div>Circadian rhythms are fundamental for maintaining physiological homeostasis, influencing processes such as sleep-wake cycles, metabolism, and hormonal regulation. The suprachiasmatic nucleus (SCN), the primary pacemaker in the brain, is necessary to maintain behavioral circadian rhythms and to synchronize peripheral clocks throughout the body in mammals. The vestibular system, responsible for balance and spatial orientation, has been implicated in circadian regulation, yet its intrinsic clock machinery remains unexplored. Previous studies suggest vestibular input influences circadian rhythms, as evidenced by altered locomotor activity and temperature control in animals with vestibular dysfunction. Additionally, vestibular disorders in humans display time-dependent patterns, further supporting a vestibular-circadian interaction. Our study investigates the presence of an autonomous circadian clock in the peripheral vestibular organs (semicircular canals SCC, saccule, utricle and vestibular ganglia) by assessing core clock gene and protein expression in vestibular structures of mice and humans. Using PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence assays from mouse tissues, we observed self-sustained oscillations in SCC, saccule, and utricle, with differential amplitudes and phase relationships. RNA scope (<em>Bmal1</em>) confirmed the rhythmic expression in the peripheral vestibular organ from mice, corroborating their functional circadian regulation. Furthermore, we explored the impact of cisplatin, a chemotherapeutic agent, on vestibular clock rhythms. Cisplatin administration disrupts PER2 oscillations in vestibular explants in a time-dependent manner, mirroring the cochlear findings where the day or night timing of drug delivery modulates drug response. Our findings provide the first direct evidence of a clock within the peripheral vestibular organ of rodents and humans, highlighting its potential role in modulating vestibular function and responses to pharmacological interventions. These findings suggest that vestibular disorders may follow a daily pattern, which could help explain why symptoms worsen or improve at different times of the day. This could lead to better treatment strategies for millions of people affected by vestibular dysfunction. Demonstrating that the chemotherapy drug cisplatin disrupts vestibular rhythms in a time-dependent manner, suggests that administering drugs at the right time of day could minimize side effects like dizziness and nausea while maximizing effectiveness. These results underscore the importance of considering circadian timing in vestibular research and therapeutic strategies.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109572"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bias-tone suppression of the auditory-nerve initial-peak (ANIP) response supports the hypothesis that ANIP is driven by cortilymph-organ-of-Corti-core longitudinal motion","authors":"John J. Guinan Jr. ,&nbsp;Hui Nam","doi":"10.1016/j.heares.2026.109575","DOIUrl":"10.1016/j.heares.2026.109575","url":null,"abstract":"<div><div>The auditory-nerve initial peak (ANIP) is the earliest response from moderate-to-high-level clicks in cat auditory-nerve type-1 fibers with characteristic frequencies (CFs) &lt;3 kHz. ANIP is inhibited by medial-olivocochlear-efferent stimulation, and is suppressed when low-frequency (50 Hz) “bias” tones place the outer-hair-cell (OHC) mechano-electric-transduction (MET) function into low-slope, saturating edges. These properties show that ANIP emanates from OHC motility. Unexpectedly, the bias-tone phase that produces the most suppression (the major-suppression phase, MSP) is opposite for ANIP versus for low-level click or tone responses. We present data showing this difference, plus this hypothesis for its origin: Low-level responses take several cycles to build up and their gain is set by the local MET-function slope; their MSP is when the bias tone quasi-statically deflects the MET operating point to its nearest low-slope, saturation edge. In contrast, ANIP is the first half-cycle response from higher-level clicks, and requires OHC stereocilia deflection only in one direction. When a bias tone places the OHC-MET operating point at its nearest saturating edge, a rarefaction-click’s unidirectional initial stereocilia deflection is <em>away from</em> this saturation, enabling a large traverse of the MET-function high-slope, high-gain region. The bias-tone level necessary to reach criterion suppression was higher for ANIP than for low-level clicks, which indicates that ANIP suppression occurred more basal where BM stiffness is higher. We hypothesize that ANIP is driven by apically-directed transverse motion of cortilymph and nearby organ-of-Corti-core tissue, i.e., is separate from the traveling-wave. Waxing-and-waning click responses also show that traveling waves are not simple, unitary waves.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109575"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovery patterns and influencing factors of temporary threshold shifts in occupational noise-exposed workers","authors":"Jing Qian ,&nbsp;Minghui Xiao ,&nbsp;Jijun Guo ,&nbsp;Danyan Cao ,&nbsp;Xuehua Wu ,&nbsp;Xiufeng Lu ,&nbsp;Linyan Shu ,&nbsp;Hairu Yang ,&nbsp;Taihua Long ,&nbsp;Aichu Yang","doi":"10.1016/j.heares.2026.109578","DOIUrl":"10.1016/j.heares.2026.109578","url":null,"abstract":"<div><div>Noise-induced hearing loss represents a significant global occupational health issue. Understanding the recovery patterns of temporary threshold shift (TTS) is crucial for early intervention. This longitudinal study enrolled 140 occupational noise-exposed workers and conducted serial audiological assessments over one week to characterize multi-frequency TTS recovery trajectories and explore influencing factors. The results showed that the highest prevalence of TTS occurred at 6 kHz (81.4%), followed by 4 kHz (72.1%). Recovery was frequency-dependent: low-frequency hearing thresholds (0.5-1 kHz) returned to baseline within 72.2 h in more than 85% of participants, while recovery at high frequencies (4-6 kHz) was comparatively slower. Longer occupational noise exposure (&gt;10 years), male, and higher noise level (≥85 dB(A)) were each associated with delayed recovery. Notably, although more than 80% of participants showed substantial hearing recovery within 72.2 h, complete recovery across all frequencies required up to one week, this suggests that the current mandated 48-h pre-audiometry rest period may be insufficient to assess full auditory recovery. We recommend extending this rest period to 72 h, with a follow-up confirmatory test one week after exposure, to provide a more evidence-based approach for occupational hearing protection protocols.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109578"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward individualized cochlear implant programming: Relating electrophysiological and psychophysical indicators of tonotopic region performance","authors":"Marlies Geys ,&nbsp;Leanne Sijgers ,&nbsp;Timona Leandra Oesch ,&nbsp;Patrick Boyle ,&nbsp;Josef Chalupper ,&nbsp;Alexander Huber ,&nbsp;Flurin Pfiffner","doi":"10.1016/j.heares.2026.109571","DOIUrl":"10.1016/j.heares.2026.109571","url":null,"abstract":"<div><div>This study compared outcomes of two electrophysiological measures, electrocochleography (ECochG) and panoramic electrically-evoked compound action potential (PECAP), and two psychophysical measures, temporal and electrode discrimination test (TED) and spectrotemporal two-octave bandpass modulation test (STM), in cochlear implant (CI) listeners. The aim was to investigate whether tonotopic regions showing poorer performance on the acoustic STM test also exhibit reduced peripheral integrity (ECochG and PECAP) or diminished modulation encoding abilities at the electrode level (TED). Twenty-seven Advanced Bionics CI candidates were prospectively enrolled prior to CI surgery. ECochG and PECAP recordings were obtained from all intracochlear electrodes intraoperatively and three months post-implantation, respectively. TED was measured via direct electrode stimulation six months post-implantation, and the STM test was conducted with CI-processed acoustic stimulation one year after surgery. All measures were obtained or averaged across four tonotopic regions. After adjusting for region-specific CI-processing differences, linear mixed model analyses showed significantly poorer STM performance in the worst-performing region compared with the other three regions (<em>p</em> &lt; 0.001). TED values were also significantly worse in this region (<em>p</em> &lt; 0.01), whereas ECochG and PECAP values did not differ significantly between the worst region on the STM test and the remaining regions. These findings demonstrate that while electrophysiological and psychophysical measures each provide valuable, spatially specific information, they capture distinct physiological and perceptual aspects of auditory processing. This highlights the need to investigating which measure, or combination of measures, can best guide individualized CI programming adjustments by identifying suboptimal performing tonotopic regions.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"473 ","pages":"Article 109571"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychoacoustic and cognitive predictors of sound sensitivity in healthy young adults","authors":"Breann Krygsman,&nbsp;Alisa Pitre,&nbsp;Sebastien Paquette","doi":"10.1016/j.heares.2026.109549","DOIUrl":"10.1016/j.heares.2026.109549","url":null,"abstract":"<div><div>Hyperacusis and sound sensitivity are complex phenomena influenced by both auditory and psychological factors. This study investigated the relationship between hearing thresholds, perceptual ratings of natural sounds, attitudes toward noise, and sex-based differences in a sample of healthy young adults. Fifty participants underwent pure-tone audiometry, completed a psychoacoustic test assessing hyperacusis (sound sensitivity), and filled out self-report questionnaires including the Youth Attitudes to Noise Scale (YANS) and the Beliefs About Hearing Protection and Hearing Loss (BAHPHL). Contrary to expectations, greater sound sensitivity was associated with lower hearing thresholds (indicating minimal hearing loss) in the low-frequency range. This suggests that preserved low-frequency hearing may contribute to auditory discomfort. Questionnaire data revealed that individuals with higher sound sensitivity also held more negative beliefs about noise and hearing protection, highlighting the role of cognitive and affective factors. No significant sex differences were found, though prior research suggests biological distinctions may still influence auditory processing. These findings underscore the importance of considering both perceptual and psychological dimensions in understanding hyperacusis.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109549"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberrubine protects against noise-induced cochlear damage and hearing loss by inhibiting the p38 MAPK signaling pathway","authors":"Hanbo Seng ,&nbsp;Guodong Hong ,&nbsp;Le Wang ,&nbsp;Yunhao Wu ,&nbsp;Peipei Li ,&nbsp;Tiancheng Zhang ,&nbsp;Yuan Zhang ,&nbsp;Xiaolong Fu ,&nbsp;Fanglei Ye","doi":"10.1016/j.heares.2026.109563","DOIUrl":"10.1016/j.heares.2026.109563","url":null,"abstract":"<div><div>Cochlear hair cells are critical sensory receptors for auditory function, and exposure to high-intensity noise can lead to irreversible hearing loss. However, the mechanisms underlying noise-induced hearing loss (NIHL) are poorly understood, and effective therapeutic strategies have yet to be developed. In this study, berberrubine (BB) was found to protect HEI-OC1 cells and hair cells of cochlear explants from hydrogen peroxide (H₂O₂)-induced damage. Furthermore, BB pretreatment protected against cochlear damage and preserved hearing in a mouse model of NIHL. Structural analysis using hematoxylin–eosin and immunofluorescence staining showed that BB pretreatment effectively protected structures such as the ribbon synapses of hair cells and the stria vascularis. In addition, BB pretreatment significantly reduced 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) levels in the cochlear hair cells following noise exposure. RNA-sequencing analyses revealed that the protective effect of BB against NIHL involved the downregulation of <em>Traf2</em> and <em>Traf6</em> in the MAPK signaling pathway, leading to reduced p38 phosphorylation and accumulation of the downstream stress biomarker Chop. This reduced reactive oxygen species (ROS) generation and inflammation in the cochlea of mice following noise exposure, thereby alleviating NIHL-related cochlear damage and protecting hearing function. In summary, our findings indicate that BB is an effective agent against NIHL, acting through regulation of the p38 MAPK signaling pathway to reduce ROS generation and inflammation in the cochlea, which may represent a novel preventive strategy.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109563"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using vocoders to the implanted ear to investigate the binaural benefit for music sound quality in single-sided deaf cochlear implant users","authors":"Sean Lang ,&nbsp;John J. Galvin III ,&nbsp;Isaac Cooley ,&nbsp;Natalia Stupak ,&nbsp;David M. Landsberger","doi":"10.1016/j.heares.2026.109548","DOIUrl":"10.1016/j.heares.2026.109548","url":null,"abstract":"<div><div>Despite the poor sound quality provided by cochlear implants (CIs), single-sided deaf (SSD) CI users prefer to listen to music with the acoustic hearing (AH) and CI ears together rather than with the AH ear alone. The source of this binaural benefit remains unclear. In the present study, sound quality ratings were collected in SSD CI users for music excerpts from different genres (pop, rock, and classical). A novel vocoder-to-the-CI (VCI) approach was used to control the spectral and temporal information delivered to the CI ear. Custom sine-wave vocoders were designed for each participant according to the frequency allocation in their clinical map. Sound quality ratings were collected with CI-only, AH-only, and CI+AH listening. CI+AH ratings were significantly higher than AH-only ratings when unprocessed stimuli or vocoded stimuli with spectro-temporal information were delivered to the CI ear. There were no significant differences among CI+AH ratings for the unprocessed stimuli, vocoded stimuli with spectro-temporal information, and vocoded stimuli with greatly reduced temporal cues, suggesting that the binaural benefit was largely driven by similar spectral information across ears. Effects of genre were minimal. CI+AH ratings for unprocessed music were significantly correlated with CI-only ratings (<em>r</em> = 0.57, <em>p</em> &lt; 0.001), with the slope (0.97) suggesting that the binaural benefit was largely additive between the AH and CI ears. VCI appears to be a fruitful approach to control the spectral and temporal information delivered to the CI ear without directly manipulating CI users’ clinical processors.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109548"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pbx1 overexpression delays cochlear hair cells degeneration in an accelerated aging mouse model","authors":"Ruihan Zhu ,&nbsp;Gaogan Jia ,&nbsp;Yiming Shen ,&nbsp;Xian Gao ,&nbsp;Yunjie Li ,&nbsp;Hua Jiang ,&nbsp;Hui Chai ,&nbsp;Mingyu Xia","doi":"10.1016/j.heares.2026.109546","DOIUrl":"10.1016/j.heares.2026.109546","url":null,"abstract":"<div><div>Age-related hearing loss (ARHL), the most prevalent sensory disorder worldwide, arises primarily from cochlear hair cells (HCs) degeneration due to aging. Although the molecular mechanisms driving HC senescence are increasingly understood<em>,</em> effective treatments for ARHL remain lacking<em>.</em> This study explores the therapeutic potential role of Pre-B cell leukemia homeobox 1 (<em>Pbx1</em>), a transcription factor involved in inner ear development and pluripotency, in mitigating ARHL. Our results reveal a striking age-dependent reduction in PBX1 expression within mouse cochlear HCs. Using D-galactose (D-gal)/lipopolysaccharide (LPS)-induced aging models in OC-1 cells and cultured cochlear explants, we demonstrated that lentiviral and adeno-associated virus (AAV)-mediated <em>Pbx1</em> overexpression significantly suppresses senescent markers and preserves HC integrity. Remarkably, in vivo delivery of <em>Pbx1</em> by AAV improved auditory function and preserved HC structure and function in ARHL mouse model. These results establish <em>Pbx1</em> as a key mediator of HC aging and a promising therapeutic target for ARHL. Our findings demonstrate that AAV-mediated <em>Pbx1</em> overexpression represents a potential therapeutic approach to prevent ARHL progression, paving the way for future clinical management of this prevalent sensory disorder.</div></div>","PeriodicalId":12881,"journal":{"name":"Hearing Research","volume":"472 ","pages":"Article 109546"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}