Sensorineural Research Articles

Association of hearing loss and risk of depression: a systematic review and meta-analysis.

Previous studies have suggested a possible link between hearing loss and the risk of depression. However, the strength of this association remains uncertain across varying follow-up periods, age groups, cohort studies, and longitudinal study designs. We conducted an extensive literature search across PubMed, Embase, and the Cochrane Library databases to retrieve pertinent studies. The quality of observational studies was assessed using the Newcastle-Ottawa Scale. Synthesis and meta-analysis of odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) were performed using Stata 14.0. Funnel plot analysis and Egger's regression test were utilized to assess potential publication bias. This meta-analysis comprised 24 cohort studies conducted between 2007 and 2024, with sample sizes ranging from 548 to 254,466 participants. Among these participants, 24,304 had experienced depression events. The pooling analysis shows that hearing loss is associated with an increased risk of depression (OR = 1.35; 95%CI: 1.27-1.44). In the subgroup analysis, the retrospective cohort exhibited a slightly higher risk of depression compared to the prospective cohort (OR = 1.43; 95% CI: 1.30-1.58). There are differences in the risk of depression among young, middle-aged, and older individuals, with older adults facing a higher risk (OR = 1.33, 95% CI: 1.21-1.45). Additionally, the risk of depression was slightly higher in the sudden sensorineural hearing loss (SSNHL) group compared to the non-SSNHL group (OR = 1.62; 95% CI: 1.27-2.07). Furthermore, in cohorts with a follow-up time ≥ 5 years, the risk of depression was higher compared to those with <5 years of follow-up (OR = 1.39; 95% CI: 1.26-1.54). Our meta-analysis shows that hearing loss increases the risk of depression. These findings provide evidence that hearing loss should be recognized as an independent risk factor for depression. https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42024502043.

Reply on: "Comment on Intratympanic Lidocaine as a Potent Remedy for Tinnitus in Sudden Sensorineural Hearing Loss: A Double-Blind, Randomized Clinical Trial".

Reply on: "Comment on Intratympanic Lidocaine as a Potent Remedy for Tinnitus in Sudden Sensorineural Hearing Loss: A Double-Blind, Randomized Clinical Trial".

Comment on: "Intratympanic Lidocaine as a Potent Remedy for Tinnitus in Sudden Sensorineural Hearing Loss: A Double-Blind, Randomized Clinical Trial".

Comment on: "Intratympanic Lidocaine as a Potent Remedy for Tinnitus in Sudden Sensorineural Hearing Loss: A Double-Blind, Randomized Clinical Trial".

Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.

Preservation of hair cells is critical for maintaining hearing function, as damage to sensory cells potentially leads to irreparable sensorineural hearing loss. Hair cell loss is often associated with inflammation and oxidative stress. One promising class of bioactive peptides is mitochondrial-derived peptides (MDPs), which have already been proven to protect various tissues from cellular stresses and delay aging processes. Humanin (HN) is one of the best-known members of this family, and recently, we have shown its protective effect in hair cells. The synthetic derivate HN S14G (HNG) has a more potent protective effect than natural HN making it a more useful peptide candidate to promote cytoprotection. A less-known MDP is small humanin-like peptide 3 (SHLP3), which has cytoprotective effects similar to HN, but likely acts through different signaling pathways. Therefore, we examined the effect of exogenous HNG and SHLP3 in auditory hair cells and investigated the molecular mechanisms involved. For this purpose, explants of the organ of Corti (OC) were treated with gentamicin in the presence and absence of HNG or SHLP3. Administration of HNG and SHLP3 reduced gentamicin-induced hair cell loss. The protective mechanisms of HNG and SHLP3 in OC explants included, in part, modulation of AKT and AMPKα. In addition, treatment with HNG and SHLP3 reduced gentamicin-induced oxidative stress and inflammatory gene overexpression. Overall, our data show that HNG and SHLP3 protect hair cells from gentamicin-induced toxicity. This offers new perspectives for the development of therapeutic strategies with MDPs against hearing loss.

Brain networks in newborns and infants with and without sensorineural hearing loss: A functional near-infrared spectroscopy study.

Understanding the impact of early sensory deficits on brain development is essential for understanding developmental processes and developing potential interventions. While previous studies have looked into the impact of prenatal experiences on language development, there is a lack of research on how these experiences affect early language and brain function development in individuals with sensorineural hearing loss (SNHL). To investigate SNHL effects on early brain development and connectivity in 4-month-olds vs healthy newborns and controls. The research involved analyzing the functional brain networks of 65 infants, categorized into three groups: 28 healthy newborns, 22 4-month-old participants with SNHL, and 15 age-matched healthy participants. The resting-state functional connectivity was measured and compared between the groups using functional near-infrared spectroscopy and graph theory to assess the brain network properties. Significant differences were found in resting-state functional connectivity between participants with SNHL and age-matched controls, indicating a developmental lag in brain connectivity for those with SNHL. Surprisingly, SNHL participants showed better connectivity development compared to healthy newborns, with connectivity strengths of 0.13 ± 0.04 for SNHL, 0.16 ± 0.08 for controls, and 0.098 ± 0.04 for newborns. Graph theory analysis revealed enhanced global brain network properties for the SNHL group, suggesting higher communication efficiency at 4 months. No significant differences were noted in network properties between 4-month-old SNHL participants and neonates. A unique pattern of central hubs was observed in the SNHL group, with 2 hubs in the left hemisphere compared to 6 in controls. 4-month-old infants with SNHL have a distinct brain network pattern with efficient long-distance information transmission but less effective local communication compared to age-matched controls.

Clinical and genetic characterisation of childhood-onset sensorineural hearing loss reveal associated phenotypes and enrichment of pathogenic founder mutations in the Finnish population

Objective To examine the clinical and genetic characteristics of childhood-onset bilateral sensorineural hearing loss (SNHL) in Finland. Design Retrospective analysis. Study sample A total of 249 children younger than 18 years were diagnosed with bilateral SNHL in Oulu University Hospital, Finland, from 2017 to 2022. Results Pathogenic or likely pathogenic gene variants or chromosome abnormalities explaining SNHL were identified in 41% (N = 101/249) of children. Likely causative variants were more commonly identified in patients with severe SNHL than in those with moderate or mild SNHL. Our study identified likely causative gene variants in 24 different genes and six different likely causative chromosome abnormalities, demonstrating the genetic heterogeneity of SNHL. Population-enriched founder mutations were identified in the CABP2, CLRN1, MYO7A, SUCLA2, TMC1, and TWNK genes. A significant number of patients had associated phenotypes, including global developmental delay or intellectual disability (16%), language disorder (20%), ophthalmological abnormalities (16%), or malformations other than those involving the ear (10%). Conclusions SNHL is genetically and clinically heterogeneous. Pathogenic variants in GJB2 were the most common. Several population-enriched variants were identified as causing SNHL in the northern Finnish population. Associated medical phenotypes are common and should be taken into account in patients’ follow-up and treatment.

Identification of a novel FGF3 variant and a new phenotype in three LAMM syndrome families

Over 700 syndromes associated with hearing loss (HL) have been identified. Labyrinthine aplasia, microtia, and microdontia (LAMM syndrome, OMIM: 610706) is a rare HL syndrome characterized by congenital sensorineural HL, labyrinthine aplasia, type I microtia and microdontia, which is caused by biallelic variants in the FGF3 gene. Using Whole-exome sequencing (WES), we identified a novel missense FGF3 variant (c.137G > C, p. Arg46Pro (NM_005247.4) in three unrelated Uyghur ethnic families. This variant is classified as a variant of uncertain significance according to ACMG guidelines, with the applied criteria of PM3, PM2_Supporting, PP3 and PP4. Patients from the three families revealed variable clinical features. We found a novel phenotype, sparse hair, in one of the proband. Our findings expanded the variant and phenotype spectrum of LAMM syndrome and provided new insights to the diagnose and pathogenesis investigation of the disease.

A Variable-Stimulus Distortion Product Otoacoustic Emission Screening Method to Match Cochlear Place-Specific Properties.

Distortion product otoacoustic emissions (DPOAEs) are a popular screening tool for hearing loss in specific populations (e.g., newborns). Current screening protocols use stimulus conditions that are agnostic to local mechanical properties of the cochlea and are also limited to a narrow frequency range. We have recently reported locally optimized stimulus frequency ratio and level combinations for recording DPOAEs up to stimulus frequencies of 19 kHz. In normally functioning cochlea, optimized stimuli improved the signal to noise ratios and allowed the registration of higher DPOAE levels, especially at higher frequencies. The purpose of this study was to evaluate the clinical performance of these physiologically motivated, locally appropriate, stimulus parameters for a screening application to identify the presence of hearing loss. Subjects were 24 adults with sensorineural hearing loss and 31 adults with normal hearing. The cubic DPOAE was measured and analyzed up to frequencies of 16 kHz using a range of stimulus conditions. Receiver operating characteristic curves were used to identify stimulus combinations most sensitive to screening for hearing loss. Receiver operating characteristic curves demonstrated improved test efficacy for hearing loss detection when using stimulus frequency ratios and levels that are frequency-dependent and consistent with known mechanical properties of the cochlea. We propose a new DPOAE recording paradigm (variable-stimuli DP) using stimuli aligned to local cochlear properties which may improve early and accurate detection of decline in cochlear function.

POLD3 haploinsufficiency is linked to non-syndromic sensorineural adult-onset progressive hearing and balance impairments.

Hearing impairment (HI) is a significant health concern globally, influenced by genetic and environmental factors. We had identified a homozygous pathogenic variant in POLD3 in a Lebanese patient with an autosomal congenital recessive syndromic hearing loss (MIM#620869). This variant was found at heterozygous state in the parents, who developed progressive hearing impairment around age 40. We conducted a thorough clinical and genetic assessment of sixteen family members, including physical exams, audiometry and vestibular function evaluations. Additionally, gene expression analysis of the Pold3 gene was performed in mice using RNAscope. Twelve individuals were heterozygous for the variant in POLD3, of whom eight showed bilateral adult-onset HI, typically starting around ages 40-50, and two older patients displaying unilateral vestibular weakness. Additionally, two carriers of the variant developed cancer at an early age. RNAscope confirmed Pold3 expression in auditory and vestibular neurons. Exome sequencing analysis excluded the presence of pathogenic variants in any known hearing impairment or cancer predisposition genes. We present herein, for the first time, evidence of a heterozygous pathogenic POLD3 variant associated with a novel form of autosomal dominant progressive adult-onset hearing and vestibular impairments. We also highlight the necessity for further exploration of the role of POLD3 in cancer predisposition.

Good cochlear implantation outcomes in subjects with mono-allelic WFS1-associated sensorineural hearing loss – a case series

Objective This study aimed to evaluate long-term cochlear implant (CI) outcomes in individuals with mono-allelic pathogenic variants in WFS1, which is associated with both Wolfram-like syndrome and DFNA6/14/38. Design Retrospective case series. Study sample Seven CI recipients, ranging from eight months to 58 years of age, were included in the study, including four with Wolfram-like syndrome and three with DFNA6/14/38. A total of ten cochlear implantations were performed among these subjects. Results At one-year post-implantation, a mean phoneme score of 90 ± 9% at 65 dB SPL in quiet was found, which remained stable up to ten years post-implantation with a mean phoneme score of 94 ± 6%. Despite these excellent outcomes, one subject achieved no speech recognition with CI and eventually became a non-user. This individual had a prolonged absence of auditory stimulation prior to implantation and encountered multiple challenges during rehabilitation. Conclusion Individuals with Wolfram-like syndrome or DFNA6/14/38 demonstrate consistently good outcomes following implantation, which remain stable over time. These findings affirm cochlear implantation as an effective rehabilitation option for these individuals. Furthermore, the stable and good CI outcomes contradict the suggested link between WFS1-associated sensorineural hearing loss and auditory neuropathy.

Sensorineural hearing loss in post-COVID-19 patients

&lt;b&gt;Background: &lt;/b&gt;Hearing loss (HL) is one of the most common chronic conditions after hypertension and arthritis. Mounting indices suggest that sensorineural hearing loss (SNHL) may be one of the adverse effects of severe acute respiratory syndrome coronavirus 2.&lt;br /&gt; &lt;b&gt;Objective: &lt;/b&gt;This work aimed at studying SNHL in post-COVID-19 patients, alongside with exploring the relationship between severity of the disease and degree of hearing disability.&lt;br /&gt; &lt;b&gt;Materials and methods: &lt;/b&gt;This prospective cross-sectional study was conducted at Al-Azhar University Hospitals, Cairo, Egypt. It included 100 post-COVID-19 patients selected according to the study inclusion and exclusion criteria. Pure tone audiometry was done to confirm the presence of HL and to determine its degree.&lt;br /&gt; &lt;b&gt;Results: &lt;/b&gt;Hundred patients with recent oncent hearing symptoms after documented COVID-19 infection were included. Males (71%) were more affected than females (29%). The most of our cases had bilateral moderate HL (45%). Tinnitus was the most frequently associated otological symptom (96.96%). The time of HL onset varied from days to weeks (55% had time onset between 11-30 days post-confirmed infection). Higher thresholds were detected in all frequencies of affected ears with more deterioration of hearing as frequencies increase. All degrees of HL were detected; mild, moderate, severe and profound. There was no significant correlation between severity of COVID-19 infection and severity of HL.&lt;br /&gt; &lt;b&gt;Conclusions: &lt;/b&gt;SNHL is one of the extrapulmonary complications of COVID-19. COVID-19 patients may develop hearing affection regardless the severity of the infection. It is recommended to assess hearing functions in patients after COVID-19 for early detection and proper management.

Changes of Otolith and Balance Function Related to Cochlear Implant in Hearing Loss With Inner Ear Malformations Children.

The increase of bilateral cochlear implantation (CI) in recent years has made it essential to comprehend the effects of CI on otolith function. This study aimed to investigate the development of gross motor and otolith function in patients with inner ear malformations (IEMs) using vestibular-evoked myogenic potentials (VEMPs). Overall, 78 patients with sensorineural hearing loss (SNHL) (age 5.7 ± 4.1 years) were divided into two groups based on the presence (IEM group, n = 39) or absence (control group, n = 39) of IEMs. VEMP testing was performed both before and 1-3 months after CI, and the evaluation of gross motor development was carried out. The mean ages for achieving head control and independent walking were delayed in the IEM group compared with the control group (p = 0.02). The preoperative cervical VEMP (cVEMP) and ocular VEMP (oVEMP) response rates were higher in the control group (60% and 86.95%) than in the IEM group (57.69% and 74.35%) (p < 0.05). Additionally, abnormal cVEMP was associated with delayed acquisition of independent walking (p = 0.017). Saccular and utricular functions after CI were lost by 40% and 31.75%, respectively, in patients who elicited preoperative VEMPs waveform (n = 25). Among SNHL patients, balance development is more delayed in patients of IEMs than in patients without IEMs. The cVEMP and oVEMP waveforms differed greatly between the two groups. The otolith-vestibular nerve conduction pathway can be affected by CI, potentially leading to otolith function impairment. Therefore, it is essential to assess otolith and balance functions before CI, and this evaluation should be considered an integral part of clinical practice.

Associations of Blood Lipids with the Risk and Prognosis of Sudden Sensorineural Hearing Loss: A Meta-analysis.

Patients with sudden sensorineural hearing loss (SSNHL) may lose their hearing. The relationship between SSNHL and total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels is still unclear. The association of TC, TG, HDL-C, and LDL-C levels with the risk and prognosis of SSNHL was explored in this study. After searching for literature in different databases, 13 researches were used to summarize the risk and prognosis of SSNHL associations with TC, TG, HDL-C, and LDL-C using meta-analysis. Total cholesterol had a significant association with the risk of SSNHL (95% CI, 1.34-2.91). Adjustment for confounding factors and grouping criteria of TG were all significant sources of heterogeneity. One of the significant sources of heterogeneity in the LDL-C subgroup analyses was an adjustment for confounders. Sensitivity analysis revealed a robust association between TC and the risk of SSNHL. There was a significant publication bias in the association between TC and SSNHL prognosis High TC level is a risk factor for SSNHL.

Prognostic Significance of Early Posttreatment Audiometry in Idiopathic Sudden Sensorineural Hearing Loss.

This study aimed to assess the prognostic value of early posttreatment initiation audiometry findings in patients with idiopathic sudden sensorineural hearing loss (ISSHL). A retrospective cohort study. The study was conducted at a single tertiary medical center. A review was conducted on 299 ISSHL patients treated between 2007 and 2023. Patients underwent audiometry on Days 2 to 3 and 5 to 7 posttreatment initiation. Data on demographics, medical history, audiometry results, and prognosis were collected. Prognosis was categorized based on hearing recovery at 1 year postdiagnosis. Older age, worse initial speech reception threshold (SRT), ischemic heart disease, cerebrovascular accidents/transient ischemic attacks, hypertension, and diabetes were associated with a poorer prognosis. Posttreatment initiation audiometry findings on Days 2 to 3 and 5 to 7 significantly correlated with prognosis. Patients with a ≥30% improvement had substantial or complete recovery in over 80% of cases, while those with <10% had <30% recovery. Multivariate analysis identified a significant improvement on days 5 to 7 as an independent predictor of complete recovery (odds ratio = 4.25 [95% confidence interval 1.96-9.23], P = .0002). Posttreatment initiation audiometry findings, particularly on Days 5 to 7, hold significant prognostic value in ISSHL patients. A substantial improvement during this timeframe is strongly associated with favorable outcomes. These findings emphasize the potential of posttreatment initiation audiometry as a valuable tool for clinicians in counseling patients with ISSHL.

Predictors of Abnormal MRI Findings in Patients with Asymmetrical Sensorineural Hearing Loss.

This study aimed to determine the predictive factors of abnormal MRI findings in patients with asymmetrical sensorineural hearing loss (ASNHL). A retrospective review of medical records. A tertiary care hospital. Patients with asymmetries of ≥10 dB in at least 1 frequency, who underwent an MRI study of the temporal bone or brain during 2019-2021, were included. Age, sex, clinical symptoms, past medical history, and audiometric parameters, including pure tone thresholds, speech reception thresholds, and speech discrimination scores, were retrieved from the electronic database. The MRI findings reported by radiologists were reviewed and extracted. Of 390 patients, 50 (12.8%) patients had relevant abnormal MRI findings that could explain ASNHL. The most prevalent abnormal MRI finding was an internal acoustic canal (IAC) or cerebellopontine angle (CPA) tumor (n = 38; 76.0%), with other notable abnormalities including labyrinthitis, stroke, mucocele, and epidermoid. Multiple logistic regression analysis highlighted that hearing asymmetry of 15 dB at 1000 Hz (OR = 4.8; 95% CI 2.2-10.5) was a significant variable. The proposed predictor demonstrated 84% sensitivity and 48% specificity in detecting abnormal MRI findings. A hearing asymmetry of 15 dB at 1000 Hz was an important clinical predictor of abnormal MRI findings in patients with ASNHL. This finding has the potential to serve as a referral guide for further MRI investigations. Level 3 Laryngoscope, 2024.

Antiviral Therapy for Congenital Cytomegalovirus Infection: Does It Prevent Late-Onset Sensorineural Hearing Loss?

Abstract Background Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensorineural hearing loss (SNHL) in children. While SNHL is often present at birth, as many as 20% of infants with congenital CMV infection may develop late-onset hearing loss beyond the neonatal period. Antiviral therapy improves hearing outcomes, but its effect on the occurrence of late-onset SNHL is not fully known. The objective is to describe the prevalence of SNHL at birth and late SNHL among infants and children with congenital CMV infection and assess the impact of antiviral treatment on the occurrence of late-onset SNHL. Methods From 2013 to 2022, infants with congenital CMV infection referred to the NEO-ID Clinic at Nationwide Children’s Hospital (NCH), Columbus, OH underwent complete evaluation including hearing testing. Pertinent demographic, clinical, audiologic, laboratory, and radiographic data were obtained and stored using an electronic database (REDCap). Infants with SNHL at birth or who developed late-onset SNHL beyond a month of age were identified and compared with respect to receipt of antiviral therapy in the neonatal period. Results During the 10-year study period, we enrolled 204 infants with congenital CMV infection: 75% (154/204) had symptomatic disease, while 25% (50/204) had clinically inapparent infection (normal physical examination, growth parameters, and evaluation). Overall, 30% (n=62) had SNHL at birth or on follow-up audiologic evaluation with the majority (95%, 59/62) having symptomatic disease. Of the 62 infants with SNHL, 29% (n=18) had late-onset SNHL in one (n=10) or both (n=8) ears at a median age of 19 months (IQR, 8.5-42 months). Of the 122 infants who received antiviral therapy initiated in the first month of age, 12 (10%) developed late-onset SNHL in one (n=7) or both (n=5) ears. All 12 had symptomatic congenital CMV infection, and 2 received cochlear implants in one ear. Of the 82 infants who did not receive any antiviral therapy, 6 (7%) developed late-onset SNHL (3, unilateral [2, symptomatic]; 3, bilateral [1, symptomatic]) and 2 received cochlear implant. There was no difference in the occurrence of late-onset SNHL in treated (10%) vs. untreated (7%) infants with congenital CMV infection (p=0.6). Conclusion In this cohort of mostly symptomatic infants with congenital CMV infection, antiviral treatment did not reduce the occurrence of late-onset SNHL. Further study on the impact of early antiviral therapy on severity of the SNHL is urgently needed to inform optimal treatment management.

Sensorineural hearing loss in Lyme neuroborreliosis

Background Sensorineural hearing loss (SNHL) has been suggested to occur in patients with Lyme neuroborreliosis (LNB); however, a clear association has never been documented. The present study prospectively investigated the development of SNHL in patients admitted for treatment of LNB using distortion-product-oto-acoustic emissions (DPOAE) as a measure of cochlear function. Methods DOAE were measured in patients with LNB on the day of diagnosis, during treatment, and 30–60 days after discharge. Frequencies were categorized as Low (1, 1.5, 2 kHz), Mid (3, 4, 5 kHz), Mid-high (6, 7, 8 kHz), and High (9, 10 kHz). Pure Tone Audiometry (PTA3) was performed at discharge and 60 days after. Patients were treated with i.v. ceftriaxone or oral doxycycline for 14 days according to guidelines. Results DPOAE measurements were obtained in 25 patients with LNB at admission and in 18 patients at follow-up. Median age was 56 years (IQR, 48–64 years), and 16 (67%) were men. Fourteen (78%) of 18 patients showed improvement in Emission Threshold Levels (ETL) from admission to follow-up in low, mid-, and mid-high frequency categories, where ETLs increased by median levels of 3.2 (−4.1 to 8.3), 7.5 (−2.8 to 9.8), and 4.7 dB (−4.3 to 10.1). A decline was observed in the high frequency category, median −3.3 dB (−9.1 to 6.7). SNHL defined by pure tone average (PTA3) >20 dB was present in 11 out of 23 (48%) at discharge and in 9 out of 16 patients (56%) 60 days after discharge, which differed significantly from matched controls (Mann-Whitney test, p = 0.036). Conclusion LNB can lead to cochlear outer-hair cell dysfunction, resulting in temporary and long-term SNHL.

Biallelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.

Combined oxidative phosphorylation deficiency (COXPD) is a rare multisystem disorder which is clinically and genetically heterogeneous. Genome sequencing identified biallelic MRPL49 variants in individuals from five unrelated families with presentations ranging from Perrault syndrome (primary ovarian insufficiency and sensorineural hearing loss) to severe childhood onset of leukodystrophy, learning disability, microcephaly and retinal dystrophy. Complexome profiling of fibroblasts from affected individuals revealed reduced levels of the small and, a more pronounced reduction of, the large mitochondrial ribosomal subunits. There was no evidence of altered mitoribosomal assembly. The reductions in levels of OXPHOS enzyme complexes I and IV are consistent with a form of COXPD associated with biallelic MRPL49 variants, expanding the understanding of how disruption of the mitochondrial ribosomal large subunit results in multi-system phenotypes.

Cochlear implant/MXene-based electroacoustic stimulation modulates the growth and maturation of spiral ganglion neurons

Cochlear implantation (CI) offers a dependable treatment for sensorineural hearing loss, with precision electroacoustic stimulation parameters showing great potential in improving auditory outcomes in CI patients. Here, we report the attachment of MXene into CI systems which effectively mimic the neural electrode interface due to MXene's excellent electrical conductivity and biocompatibility. Low-frequency short-term biphasic electrical pulses emitted by the MXenes-based CI promoted the outgrowth of spiral ganglion neuron (SGN) neurites and growth cones, substantially boosting the calcium activity in SGNs. This study lays a theoretical foundation for the precision medicine approaches in CI patient care, and informs the selection of materials for cochlear implant electrode materials in the future.

Early transtympanic administration of rhBDNF exerts a multifaceted neuroprotective effect against cisplatin-induced hearing loss.

Cisplatin-induced sensorineural hearing loss is a significant clinical challenge. Although the potential effects of brain-derived neurotrophic factor (BDNF) have previously been investigated in some ototoxicity models, its efficacy in cisplatin-induced hearing loss remains uncertain. This study aimed to investigate the therapeutic potential of recombinant human BDNF (rhBDNF) in protecting cells against cisplatin-induced ototoxicity. Using an in vivo model of cisplatin-induced hearing loss, we investigated the beneficial effects of transtympanic administration of rhBDNF in a thermogel solution on hearing function and cochlear injury, using electrophysiological, morphological, immunofluorescence and molecular analyses. Our data showed that local rhBDNF treatment counteracted hearing loss in rats receiving cisplatin by preserving synaptic connections in the cochlear epithelium and protecting hair cells (HCs) and spiral ganglion neurons (SGNs) against cisplatin-induced cell death. Specifically, rhBDNF maintains the balance of its receptor levels (pTrkB and p75), boosting TrkB-CREB pro-survival signalling and reducing caspase 3-dependent apoptosis in the cochlea. Additionally, it activates antioxidant mechanisms while inhibiting inflammation and promoting vascular repair. Collectively, we demonstrated that early transtympanic treatment with rhBDNF plays a multifaceted protective role against cisplatin-induced ototoxicity, thus holding promise as a novel potential approach to preserve hearing in adult and paediatric patients undergoing cisplatin-based chemotherapy.