Search Results (209)

Background: Sensorineural hearing loss (SNHL) is increasingly recognized as a disorder involving not only hair-cell damage but also selective degeneration of spiral ganglion neurons (SGNs). Recent single-cell, molecular, and functional studies have refined the classical type I/type II classification of SGNs by identifying distinct Ia, Ib, and Ic subtypes within type I neurons. This review aims to synthesize current evidence on how SGN vulnerability is shaped by the interaction between subtype identity, life stage, and injury context. Methods: We conducted a critical narrative review of recent studies on SGN heterogeneity and subtype-specific vulnerability across development, maturity, and aging, with particular attention to molecular profiling, functional studies, and emerging therapeutic strategies. Results: SGN degeneration in SNHL is not uniform. During development, the available evidence mainly supports the vulnerability of subtype specification, synaptogenesis, and activity-dependent maturation, rather than direct selective degeneration of mature Ia/Ib/Ic identities. In the mature cochlea, subtype-specific differences in synaptic architecture, ion-channel composition, and metabolic demand appear to shape responses to noise, ototoxic drugs, and ischemic stress, with Ic-related populations often showing greater vulnerability. During aging, cumulative mitochondrial dysfunction, oxidative stress, chronic inflammation, and declining neurotrophic support may progressively unmask differences in subtype resilience and contribute to age-related auditory decline. Conclusions: A lifespan-oriented and subtype-informed framework may improve the current understanding of selective SGN degeneration and support the development of more precise neuroprotective and reparative strategies for SNHL. Full article

Presbycusis, or age-related hearing loss (ARHL), is a multifactorial disorder characterized by a gradual, bilateral sensorineural decline in hearing sensitivity, predominantly affecting high-frequency sounds. It is one of the most common chronic conditions in the aging population and represents a major public health concern due to its high prevalence and progressive nature. Presbycusis significantly impairs speech perception, especially in noisy environments, leading to communication difficulties, reduced social participation, increased risk of social isolation, and a decline in quality of life. Moreover, growing evidence highlights a strong association between ARHL and cognitive impairment, dementia, depression, and increased frailty in older adults. The etiology of presbycusis is complex and involves the interplay between genetic predisposition and cumulative environmental and lifestyle-related factors. Genetic susceptibility influences cochlear aging, neural degeneration, and vulnerability to external insults. Non-genetic contributors include chronic noise exposure, cardiovascular and metabolic disorders such as diabetes and dyslipidemia, ototoxic medications, smoking, and other lifestyle factors that may accelerate cochlear damage through oxidative stress and microvascular dysfunction. This narrative review aims to provide an updated overview of the genetic and environmental determinants involved in the development and progression of presbycusis. Furthermore, it discusses the clinical implications of these factors for early identification, audiological evaluation, prevention strategies, and personalized management approaches. A better understanding of the multifactorial nature of presbycusis may support the development of targeted interventions to preserve hearing function and improve overall health outcomes in the aging population. Full article

Background: Amikacin remains a key agent in the treatment of severe and complicated infections due to its bactericidal activity and low risk of Clostridioides difficile infection. It retains activity against most aerobic Gram-negative bacteria, including multidrug-resistant Enterobacterales and Pseudomonas. However, its use is limited by nephrotoxicity and ototoxicity. Methods: This narrative review evaluates clinical indications, pharmacokinetic and pharmacodynamic properties, dosing strategies, therapeutic drug monitoring (TDM), and safety profile of amikacin in adult patients based on 56 selected publications. A total of 24 articles were identified through database searches (PubMed and Embase), complemented by 32 additional sources to provide clinical and pharmacological context. Results: Available evidence demonstrates considerable uncertainty regarding the comparative effectiveness of different monitoring strategies. Lower trough concentrations are generally associated with reduced nephrotoxicity; however, an optimal safety threshold has not been clearly established. Guideline-recommended targets vary substantially and are supported by low-quality evidence. Amikacin pharmacokinetics, tissue penetration and toxicity are influenced by patient-specific factors, including critical illness, renal function variability, and concomitant nephrotoxic therapy, particularly vancomycin. Ototoxicity remains an additional clinically relevant concern. Conclusions: Current evidence suggests that uniform dosing and monitoring paradigms are insufficient. Patient-tailored strategies integrating TDM and mitigation of modifiable risk factors are required. Prospective studies comparing monitoring regimens are needed to optimize the safe clinical use of amikacin and inform future guideline development. Full article

Cisplatin-induced ototoxicity is a permanent, bilateral sensorineural hearing loss occurring in up to 80% of treated patients. Its defining and clinically challenging feature is the progressive worsening of auditory function that continues well after chemotherapy has ended, a trajectory that cannot be explained by cumulative dose alone. This article is a comprehensive review of the present research studies on mechanisms that are responsible for this post-treatment progression. The cochlea, unlike other organs, appears to be unable to eliminate platinum (the active divalent metal ion released from cisplatin and responsible for its cytotoxic and ototoxic effects): traces of it can be found in human temporal bone tissue even more than 18 months after last infusion, and bone might serve as a long-term systemic reservoir. Within the inner ear, platinum accumulates preferentially in the stria vascularis, impairing endocochlear potential and outer hair cell function. Retained platinum sustains cascading effects including sustained NOX3-dependent oxidative stress, mitochondrial dysfunction, ongoing genotoxic injury to non-regenerative cells, and the early loss of ribbon synapses that precipitates delayed spiral ganglion neurodegeneration. Pharmacogenetic variability in platinum transport and antioxidant metabolism further modulates individual susceptibility. These findings support lifelong audiological surveillance and provide a basis for designing strategies that can protect hearing without compromising the essential anticancer efficacy of cisplatin therapy. Full article

Background/Objectives: Cisplatin-exposed pediatric cancer patients are at increased risk of ototoxicity, particularly those under 5 years of age. In this group, audiological monitoring is challenging, as interpretation of otoacoustic emissions (OAEs) and tympanometry, used to supplement behavioral audiometry, is subject to interindividual variability. This study aimed to identify key challenges and establish an international consensus on optimal testing procedures and interpretation criteria for assessing early cochlear damage. Methods: Audiological data from 11 children (<5 years) exposed to cisplatin in utero were evaluated. An international panel of 10 pediatric oncology audiology experts reviewed tympanometry, transient evoked OAEs (TEOAEs), and distortion product OAEs (DPOAEs). Areas of disagreement were analyzed, and consensus was sought regarding testing conditions, interpretation, and clinical application. Results: Agreement on cochlear status was good in 10/22 ears, moderate in 3/22 ears, and poor in 9/22 ears, highlighting substantial variability in interpretation. Consensus was achieved on minimal technical and interpretative requirements for OAE testing in this population. The panel proposes a classification framework integrating OAEs and tympanometry to guide clinical follow-up. Importantly, normal OAE results were not considered sufficient to exclude ototoxic damage or mild hearing loss. Conclusions: OAEs, particularly DPOAEs, are valuable as a screening tool in ototoxicity monitoring programs for young children, provided that testing conditions and interpretation are standardized. However, OAEs alone are insufficient for definitive assessment. Longitudinal monitoring and confirmatory testing with behavioral audiometry or ABR/ASSR remain essential. Further validation of the proposed classification system is warranted. Full article

Oncomodulin (OCM) is the most abundant Ca²⁺ buffering protein found in mature outer hair cells (OHCs). Cadherin 23 (CDH23) is a crucial component of the tip-links in hair cell stereocilia. The absence or dysfunction of these two proteins contributes to the early onset of age-related hearing loss (AHL). In this study, we investigated the effects of the Cdh23^753G→A mutation on OHC function using new Ocm-knockout (KO) mouse models (Ocm^tm1a/tm1a) with or without the Cdh23^753G→A mutation. Despite having the same genetic background, Ocm-KO mice carrying the Cdh23^753G→A mutation displayed a notable decline in OHC function across all measured frequencies as early as three months of age. In contrast, Ocm-KO mice without the Cdh23^753G→A mutation did not exhibit comparable hearing loss until they reached twelve months of age. Additionally, we examined the role of OCM in preserving OHC function under ototoxic stress induced by HPβCD (2-hydroxypropyl-β-cyclodextrin). The distortion product otoacoustic emission data show that the administration of HPβCD resulted in a more pronounced decline in OHC function in Ocm-KO mice compared to wild-type (WT) mice. Time-lapse recording also shows that HPβCD treatment led to greater structural deterioration and more rapid rupture events in OHCs from Ocm-KO mice than in those from WT mice. These findings suggest that the Cdh23^753G→A mutation, rather than other potential strain-specific genetic factors associated with AHL, significantly exacerbates the early onset of AHL phenotypes in Ocm-KO mice. Furthermore, our data indicates that the OCM protein in OHCs enhances their ability to withstand ototoxic stimuli. Full article

Sensorineural hearing loss (SNHL) can result from genetic mutations, excessive noise exposure, ototoxic drugs, and aging. Glutamate excitotoxicity is one of the underlying mechanisms of SNHL. However, the specific roles of different glutamate receptor subtypes in normal signaling and excitotoxic damage remain unclear. Addressing these questions requires relevant experimental models. This review compares existing protocols for the isolation and cultivation of primary spiral ganglion cells. It also evaluates the utility of this model for studying glutamatergic transmission and glutamate-induced excitotoxicity. A literature search was conducted in PubMed, Scopus, Google Scholar, and Web of Science. We identified 16 relevant English-language articles published since 1990, when the model was first used to study glutamatergic signaling. Our analysis reveals significant heterogeneity in spiral ganglion cell isolation protocols and culture conditions. We highlight major differences in glutamate concentrations and exposure times used to model excitotoxicity. The most significant limitation of this model is the loss of the native microenvironment of auditory neurons, including their dendritic and axonal contacts. Nevertheless, primary spiral ganglion cells serve as a suitable in vitro model for investigating auditory neuron function and pathology. The number of neurons and neurite length serve as reliable indicators of otoprotective effects under conditions of glutamate excitotoxicity. Based on an analysis of the key stages of primary SGC culture establishment, this study proposes approaches to overcome limitations and improve the practice of using this model. A better understanding of the function of glutamate receptors of SGNs and the mechanisms behind glutamate excitotoxicity could help us to develop new treatments for SNHL. This review serves as a practical guide for researchers implementing or optimizing primary SGC cultures. Full article

Ototoxicity is traditionally viewed as a local cochlear adverse effect of indispensable therapies such as cisplatin and aminoglycosides. However, emerging evidence suggests that cochlear vulnerability is shaped by systemic physiology, including inflammatory tone, vascular barrier integrity, and metabolic state. In this Review, we propose a Gut–Mito–Ear axis in which gut ecosystem function influences circulating mediator modules that converge on two cochlear mediator nodes: blood–labyrinth barrier (BLB) gating and mitochondrial stress tolerance. We synthesize evidence showing that gut perturbation can alter cochlear outcomes in vivo, that at least one microbiota-derived metabolite signal can directly protect hearing in experimental settings, and that BLB dysfunction and inflammatory trafficking are mechanistically relevant to cisplatin- and aminoglycoside-induced injury. We further organize the literature using an evidence-weighted framework that distinguishes direct cochlear causality from mechanistic plausibility and explicitly retains negative studies as boundary-setting evidence. Finally, we outline a translational roadmap in which microbiome-targeted prevention is pursued through mediator-anchored, non-interference-aware strategies and evaluated across linked state variables spanning exposure context, gut function, defined mediator modules, BLB gating, mitochondrial stress tolerance, and auditory phenotype. The Gut–Mito–Ear axis is not considered an established mechanism. We present it as a falsifiable systems-biology model that organizes the current evidence. Within this model, we define the minimum and ideal standards for A-tier causal evidence, explicit criteria for interpreting boundary-setting negative (A−) studies, and a set of testable predictions for causal validation. Full article

Ototoxicity represents a clinically significant complication of anticancer therapy in pediatric patients. Cytotoxic agents used in oncology, particularly platinum-based chemotherapy, may induce damage to the auditory and vestibular systems, resulting in hearing loss, tinnitus, and balance disturbances. Even mild hearing impairment during childhood may negatively affect speech perception, language development, communication abilities, and subsequent educational and psychosocial functioning. This narrative review aims to synthesize current evidence on treatment-related ototoxicity in children, with particular focus on commonly implicated therapies, clinical consequences, diagnostic approaches, and potential preventive strategies. A focused literature search was conducted in PubMed for publications from 2019 to 2025 addressing ototoxicity associated with pediatric anticancer treatment and audiological monitoring methods. The analysis indicates that platinum-based compounds, especially cisplatin and carboplatin, remain the primary agents associated with ototoxicity, with reported incidence ranging from approximately 20–70% for cisplatin and 10–30% for carboplatin. Additional risk factors include young age, baseline hearing status, renal function, and exposure to other ototoxic agents such as aminoglycoside antibiotics. Early detection relies on comprehensive audiological monitoring combining behavioral and objective methods, including pure-tone audiometry, extended high-frequency audiometry, otoacoustic emissions, and auditory brainstem response testing. Standardized grading systems such as ASHA, Brock, Chang, and SIOP Boston criteria play a key role in identifying and classifying ototoxic changes. Emerging research focuses on improved monitoring protocols, biomarker identification, and the development of otoprotective strategies, including sodium thiosulfate and experimental molecular therapies. Implementing systematic hearing monitoring and preventive strategies is essential to reduce long-term auditory complications and improve quality of life in pediatric cancer survivors. Full article

While cochlear implants allow restoration of sound perception in individuals with severe to profound hearing loss, there remains significant variability in patient outcomes. A potential factor that may account for this unexplained variability is the formation of fibrosis within the cochlea after implantation. This study investigated the therapeutic potential of pirfenidone (PFD) in preventing cochlear implant-induced fibrosis and compared outcomes with dexamethasone (DEX) treated animals. The utility of PFD was determined in cultures of fibrocytes isolated from the inner ear of guinea pigs. Specifically, PFD-treatment significantly reduced p38 MAPK signalling, fibrocyte cell proliferation, migration and collagen III deposition in response to pro-fibrotic stimuli. In a guinea pig model, local hydrogel-mediated delivery of PFD to the round window at the time of implant surgery significantly reduced the amount of tissue reaction measured by micro-computed tomography at two months post-implantation (p = 0.0297). Specifically, a 40% decrease in implant-induced tissue reaction was observed in PFD-treated animals compared to vehicle-treated controls. Notably, no evidence of ototoxicity was observed following PFD-treatment. In contrast, a 36% decrease in the amount of tissue reaction was measured in the DEX-treated control group (p = 0.0436). Overall, these data demonstrate that PFD shows significant therapeutic potential in reducing cochlear implant-induced fibrosis. Full article

To evaluate the potential ototoxic effects of lactoferrin on the inner ear using electrophysiological and histological methods. Methods: Thirty-two Sprague-Dawley rats (64 ears) were divided into four groups: control, saline, antiseptic solution (70% isopropyl alcohol + 2% chlorhexidine), and lactoferrin. Groups II–IV received three intratympanic injections. Auditory brainstem response (ABR) tests were performed at baseline, day 7, and day 21. Cochlear histology and VEGF immunoreactivity were assessed. Results: Baseline hearing was similar across groups. Post-treatment, Groups II and IV showed partial recovery at 8, 16, and 24 kHz, while Groups III and IV had worsening thresholds at higher frequencies. Histologically, Group IV’s cochlear structures remained largely intact. VEGF immunoreactivity was severe to moderate in Groups I, II, and IV, and weaker in Group III. Conclusions: Lactoferrin showed relative safety at lower frequencies but possible ototoxicity at higher frequencies. However, no significant structural damage was observed in cochlear tissues. Full article

Background/Objectives: Nasopharyngeal cancer (NPC) is prevalent in Southeast Asia, Southern China and North Africa. Up to 46% of NPC patients undergoing cisplatin chemoradiation treatment experience irreversible hearing loss. Prestin is a motor protein in the outer hair cells of the cochlea, and animal studies have shown that blood prestin levels are elevated following cisplatin induced hearing loss. We investigated whether rising serum prestin levels can predict sensorineural hearing loss (SHNL) in NPC patients undergoing induction cisplatin chemotherapy (icCRT). Methods: Serum prestin levels were measured at ten time points during cisplatin chemotherapy. Pure tone audiogram and tinnitus handicap inventory (THI) were measured at baseline and at one and nine months after cisplatin administration. These outcomes were obtained to investigate whether rising prestin levels predict SNHL or worsening THI. Results: Of the 11 patients accrued, there was no association between prestin level and SNHL. An increase in THI was associated with higher prestin levels. There was significant hearing loss at 8 kHz at one (right ear, p = 0.012, left ear, p = 0.043) and nine months (right ear, p = 0.011) after treatment. After completing cisplatin, patients also had increased THI. Conclusions: Prestin was not identified as a biomarker of cisplatin-induced hearing loss in our cohort of NPC patients undergoing icCRT. NPC patients experience worsening of tinnitus with cumulative cisplatin, and hearing loss can persist at nine months post treatment. Future studies should focus on improved novel methods for measuring prestin or other cochlear proteins to better identify potential markers before permanent cisplatin induced hearing loss. Full article

Autophagy plays a key role in the development and homeostasis of the cochlear organ. Alterations in the autophagic pathways have been associated with damage to auditory cell types and hearing impairment caused by an array of factors like age, ototoxicity, exposure to high levels of noise, or genetic mutations. Cochlear damage frequently entails mitochondrial dysfunction, impaired mitophagy and the accumulation of high concentrations of free radicals. This review summarizes the observations made to date on the autophagic function in response to cochlear damage and the results of either activating or inhibiting these processes. The data demonstrate that autophagic activity is cell context-dependent and varies according to the cochlear cell type, the toxic agent, its levels and the length and timing of its administration; other factors that influence the autophagic response may be external to the auditory system or related to epigenetic changes or the expression of genetic variants. Modulation of the autophagic status has an effect on auditory cell loss and the progression to hearing impairment and this approach has thus become a promising avenue towards the protection of the hearing function. Nonetheless, this is no easy task and it will require the identification of reliable biomarkers to evaluate the dynamics of autophagic activity as well as the development of specific autophagy modulators that do not exert toxicity. Full article

Background/Objectives: Coenzyme Q10 (CoQ10) is crucial for mitochondrial bioenergetics and redox balance and has been studied in hearing disorders. Its clinical use ranges from genetic mitochondrial deafness to acquired hearing loss associated with oxidative stress. This review aimed to map human clinical evidence on CoQ10 in hearing issues and differentiate its therapeutic roles based on underlying causes. Methods: This review was conducted following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). A systematic search of PubMed, Europe PubMed Central, the Directory of Open Access Journals (DOAJ), and ClinicalTrials.gov was performed. Human clinical studies evaluating CoQ10 or water-soluble CoQ10 formulations with hearing-related outcomes were included and synthesized descriptively. Results: Fourteen studies met the inclusion criteria, including randomized controlled trials, non-randomized clinical studies, case series, and case reports. Two distinct therapeutic roles of CoQ10 emerged: in primary mitochondrial hearing disorders caused by defects in mitochondrial DNA or CoQ10 biosynthesis pathways, CoQ10 acted as a replacement therapy and was consistently linked to stabilization or prevention of progressive sensorineural hearing loss. Conversely, in acquired or age-related conditions—including presbycusis, noise-induced hearing loss, ototoxicity, tinnitus, and sudden sensorineural hearing loss—CoQ10 was used as an antioxidant or neuroprotective supplement, with outcomes showing functional preservation, symptom reduction, or decreased cochlear injury. Internal validity varied across studies: most evidence for replacement therapy was derived from observational designs, and antioxidant applications were mainly supported by small or preliminary clinical trials. Conclusions: The available evidence suggests two distinct clinical roles of CoQ10 in hearing disorders: (i) replacement therapy in genetically defined mitochondrial deafness and (ii) adjunctive antioxidant/neuroprotective use in acquired conditions. Given heterogeneity and limited study quality, further well-designed trials are needed before broad clinical recommendations can be made. Full article