Treatment Of Sensorineural Hearing Loss Research Articles

Additional comments on foot reflexology treatment for sensorineural hearing loss in infant.

Currently, treatment options for infant sensorineural hearing loss (SNHL) are limited. This article describes a novel case of SNHL in an infant successfully treated with foot reflexology, along with observed brain activity changes before and after treatment, as indicated by functional magnetic resonance imaging. Hence, this commentary discusses the case and our viewpoints regarding foot reflexology for treating SNHL.

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.

Ototoxicity-Alleviating and Cytoprotective Allomelanin Nanomedicine for Efficient Sensorineural Hearing Loss Treatment.

Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.

Silencing of TXNIP attenuates oxidative stress injury in HEI-OC1 by inhibiting the activation of NLRP3 and NF-κB

Sensorineural hearing loss (SNHL) is the most common type of hearing loss worldwide. The primary mechanism is oxidative injury to the cochlea as a result of oxidative stress. Therefore, exploring antioxidant strategies is particularly important in addressing SNHL.Thioredoxin-interacting protein (TXNIP) is an upstream target of oxidative stress-induced damage, and the NOD-like receptor protein 3 (NLRP3) and NF-κB pathways may be the main downstream molecular pathways, but this has not been reported in SNHL. Therefore, we investigated the molecular mechanism and role of TXNIP in oxidative stress injury induced by H2O2 in the HEI-OC1 auditory cells. To induce oxidative stress, HEI-OC1 cells were treated with H2O2. The TXNIP expression was measured by western blotting and Immunofluorescence. Intracellular TXNIP was knocked down using small interfering RNAs (siRNAs). Cell viability was measured by CCK8, total intracellular reactive oxygen species (ROS) by DCFH-DA, mitochondrial ROS by Mito-SOX, NLRP3, pro-caspase-1, total p65 NF-κB, and phospho-p65 NF-κB expression were measured by western blotting. Statistical analyses were performed using one-way analysis of variance, and p < 0.05 was considered statistically significant. We found that H2O2 treatment induced oxidative stress injury in HEI-OC1 cells, as evidenced by decreased cell viability and increased total intracellular and mitochondrial ROS levels (p < 0.05). TXNIP expression was elevated, and NLRP3 and NF-κB were activated (p < 0.05). Moreover, siRNA-TXINIP co-treatment reversed these changes and protected HEI-OC1 cells from oxidative stress (p < 0.05). We concluded that H2O2-induced oxidative stress in HEI-OC1 cells was alleviated by TXNIP inhibition. The finding may provide new insight into the prevention and treatment of SNHL.

Construction of organ of Corti organoid to study the effects of berberine sulfate on damaged auditory cells.

Sensorineural hearing loss (SNHL) is mainly caused by injury or loss of hair cells (HCs) and associated spiral ganglion neurons (SGNs) in the inner ear. At present, there is still no effective treatment for SNHL in clinic. Recently, advances in organoid bring a promising prospect for research and treatment of SNHL. Meanwhile, three-dimensional (3D) printing provides a tremendous opportunity to construct versatile organoids for tissue engineering and regenerative medicine. In this study, gelatin (Gel), sodium alginate (SA), and polyvinyl alcohol (PVA) were used to fabricate biomimetic scaffold through 3D printing. The organ of Corti derived from neonatal mice inner ear was seeded on the PVA/Gel/SA scaffold to construct organ of Corti organoid. Then, the organ of Corti organoid was used to study the potential protective effects of berberine sulfate on neomycin-juried auditory HCs and SGNs. The results showed that the PVA/Gel/SA biomimetic 3D scaffolds had good cytocompatibilities and mechanical properties. The constructed organoid could maintain organ of Corti activity well in vitro. In addition, the injury intervention results showed that berberine sulfate could significantly inhibit neomycin-induced HC and SGN damage. This study suggests that the fabricated organoid is highly biomimetic to the organ of Corti, which may provide an effective model for drug development, cell and gene therapy for SNHL.

Outcomes following cochlear implantation with eluting electrodes: A systematic review

AbstractObjectivesTo establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes.MethodsSystematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug‐eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement.ResultsSearches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin‐like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin‐3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non‐eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post‐implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post‐implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies.ConclusionsEluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in‐human studies will be required to determine the clinical usefulness of drug‐eluting cochlear implants as a future treatment for sensorineural hearing loss.

A silk-based hydrogel containing dexamethasone and lipoic acid microcrystals for local delivery to the inner ear

Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.

A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss

Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change −0.87 dB; 95% CI −2.37 to 0.63; P = 0.252 and −0.46 dB; 95% CI −1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial’s primary endpoint was not met.

Gelatin-Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise-Induced Hearing Loss.

Nanoparticle-based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug-delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise-induced hearing loss via loading epigallocatechin gallate (EGCG) with anti-lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell-particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG-loaded nanosystem (TDN-EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN-EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial

ObjectiveTo determine if valganciclovir initiated after 1 month of age improves congenital cytomegalovirus (cCMV(-associated sensorineural hearing loss (SNHL). Study designWe conducted a randomized, double-blind, placebo-controlled phase 2 trial of 6 weeks of oral valganciclovir at United States (n=12) and United Kingdom (n=9) sites. Patients ages1 month through 3 years with baseline SNHL were enrolled. The primary outcome was change in total ear hearing between baseline and study month 6. Secondary outcome measures included change in best ear hearing and reduction in CMV viral load in blood, saliva, and urine. ResultsOf 54 participants enrolled, 35 were documented to have cCMV infection and were randomized (active group: 17; placebo group: 18). Mean age at enrollment was 17.8 ± 15.8 months (valganciclovir) versus 19.5 ± 13.1 months (placebo). Twenty (76.9%) of the 26 ears from subjects in the active treatment group did not have worsening of hearing, compared with 27 (96.4%) of 28 ears from subjects in the placebo group (p= 0.09). All other comparisons of total ear or best ear hearing outcomes were also not statistically significant. Saliva and urine viral loads decreased significantly in the valganciclovir group but did not correlate with change in hearing outcome. ConclusionsIn this randomized controlled trial, initiation of antiviral therapy beyond the first month of age did not improve hearing outcomes in children with cCMV-associated SNHL.

Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.

Hearing loss places a significant burden on our aging population. However, there has only been limited progress in developing therapeutic techniques to effectively mediate this condition. This review will outline several of the most commonly utilized practices for the treatment of sensorineural hearing loss before exploring more novel techniques currently being investigated via both in vitro and in vivo research. This review will place particular emphasis on novel gene-delivery technologies. Primarily, it will focus on techniques used to deliver genes that have been shown to encourage the proliferation and differentiation of sensory cells within the inner ear and how these technologies may be translated into providing clinically useful results for patients.

Research progress of neural stem cells in the treatment of sensorineural hearing loss

Research progress of neural stem cells in the treatment of sensorineural hearing loss

Association between gut microbiota and sensorineural hearing loss: a Mendelian randomization study.

Several recent studies speculated that the gut microbiota is associated with sensorineural hearing loss (SNHL) and proposed the concept of the gut-inner ear axis. However, the causal effect of gut microbiota on SNHL is still unknown. In this study, we performed a two-sample Mendelian randomization (MR) analysis to estimate the causal effect of gut microbiota on SNHL. Gut microbiota data were obtained from the largest available genome-wide association study (n = 18,340) conducted by the MiBioGen consortium. The summary statistics of SNHL were obtained from the FinnGen consortium R8 release data (28,310 cases and 302,750 controls). The causal effects were estimated with inverse-variance weighted, MR-Egger, and weighted median. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be associated with SNHL in forward Mendelian randomization analysis. We then performed sensitivity analyses, including Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, cML-MA-BIC, and leave-one-out analysis, to detect heterogeneity and pleiotropy. The inverse-variance weighted results suggested that Lachnospiraceae (UCG001) had a significant protective effect against SNHL (odds ratio = 0.85, 95% confidence interval: 0.78-0.93, P = 6.99 × 10-4). In addition, Intestinimonas (odds ratio = 0.89, 95% confidence interval: 0.82-0.97, P = 8.53 × 10-3) presented a suggestively protective effect on SNHL. Rikenellaceae (RC9gutgroup) (odds ratio = 1.08, 95% confidence interval: 1.02-1.15, P = 0.01) and Eubacterium (hallii group) (odds ratio = 1.12, 95% confidence interval: 1.00-1.24, P = 0.048) suggestively increase the risk of SNHL. The results of the reverse MR analysis showed that there is no significant causal effect of SNHL on the gut microbiota. No significant heterogeneity of instrumental variables or pleiotropy was detected. The evidence that the four genera mentioned above are associated with SNHL supports the hypothesis of a gut-inner ear axis. Our study provides microbial markers for the prevention and treatment of SNHL, and further studies are needed to explore the mechanisms of the gut microbiome-inner ear axis in health and diseases.

A Straightforward Method to Produce Multi-Nanodrug Delivery Systems for Transdermal/Tympanic Patches Using Electrospinning and Electrospray.

The delivery of drugs through the skin barrier at a predetermined rate is the aim of transdermal drug delivery systems (TDDSs). However, so far, TDDS has not fully attained its potential as an alternative to hypodermic injections and oral delivery. In this study, we presented a proof of concept of a dual drug-loaded patch made of nanoparticles (NPs) and ultrafine fibers fabricated by using one equipment, i.e., the electrospinning apparatus. Such NP/fiber systems can be useful to release drugs locally through the skin and the tympanic membrane. Briefly, dexamethasone (DEX)-loaded poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fiber meshes were decorated with rhodamine (RHO)-loaded poly(lactic-co-glycolic acid) (PLGA) NPs, with RHO representing as a second drug model. By properly tuning the working parameters of electrospinning, DEX-loaded PHBHV fibers (i.e., by electrospinning mode) and RHO-loaded PLGA NPs (i.e., by electrospray mode) were successfully prepared and straightforwardly assembled to form a TDDS patch, which was characterized via Fourier transform infrared spectroscopy and dynamometry. The patch was then tested in vitro using human dermal fibroblasts (HDFs). The incorporation of DEX significantly reduced the fiber mesh stiffness. In vitro tests showed that HDFs were viable for 8 days in contact with drug-loaded samples, and significant signs of cytotoxicity were not highlighted. Finally, thanks to a beaded structure of the fibers, a controlled release of DEX from the electrospun patch was obtained over 4 weeks, which may accomplish the therapeutic objective of a local, sustained and prolonged anti-inflammatory action of a TDDS, as is requested in chronic inflammatory conditions, and other pathological conditions, such as in sudden sensorineural hearing loss treatment.

Sustained delivery of triamcinolone acetonide from a thermosensitive microemulsion gel system for the treatment of sensorineural hearing loss

Intratympanic administration for the delivery of steroids has been extensively studied but limited because of low permeability of the drug through the row window membrane. Here, to effectively deliver poorly soluble triamcinolone acetonide (TA), microemulsions (ME) were prepared from Capmul MCM (oil), Cremophor RH40 (surfactant), and tetraglycol (cosurfactant) based on solubility studies, emulsifying ability test, and pseudoternary phase diagrams. Microemulsion gel (MEG) was prepared by mixing TA-ME with a poloxamer hydrogel base. The physicochemical properties of ME and MEG formulations were characterized, and the toxicity and oto-protective effectiveness were evaluated in vitro and in vivo. The ME-3 formulation showed a small droplet size (16.5 ± 0.2 nm), narrow PDI (0.067 ± 0.041), and enhanced TA solubility (2619.7 ± 57.6 μg/g). The optimized MEG demonstrated temperature-dependent gelation with a gelation time of 208 ± 10 sec at 37 °C. Slow degradation of the gel matrix sustained release of TA from MEG compared to the ME formulation. Both TA-ME and TA-MEG were found to be nontoxic to NIH3T3 cells at the test concentrations (0 to 5 µg/mL), and biocompatible after intratympanic administration to mice. The incorporation of ME into thermosensitive hydrogels prolonged retention of TA at the site of administration until 6 days. As a consequence, the enhanced drug absorption into the cochlea in TA-MEG group (approximately 2 times higher than other groups) protected hair cells, spiral ganglion neurons, and stria vascular cells from cisplatin-induced damage. Therefore, this injectable TA-loaded MEG is an effective and safe vehicle for the sustained delivery of triamcinolone acetonide into the inner ear.

Injury and protection of spiral ganglion neurons.

Cochlear spiral ganglion neurons (SGNs) are bipolar ganglion cells and are the first neurons in the auditory transduction pathway. They transmit complex acoustic information from hair cells to second-order sensory neurons in the cochlear nucleus for sound processing. Injury to SGNs causes largely irreversible hearing impairment because these neurons are highly differentiated cells and cannot regenerate, making treatment of sensorineural hearing loss (SNHL) arising from SGN injury difficult. When exposed to ototoxic drugs or damaging levels of noise or when there is loss of neurotrophic factors (NTFs), aging, and presence of other factors, SGNs can be irreversibly damaged, resulting in SNHL. It has been found that NTFs and stem cells can induce regeneration among dead spiral ganglion cells. In this paper, we summarized the present knowledge regarding injury, protection, and regeneration of SGNs.

Inner ear therapeutics and the war on hearing loss: systemic barriers to success.

Despite over 20 years of effort in academic research centers, start-up companies, and established pharmaceutical companies, there are no FDA-approved inner ear therapeutics for treatment of sensorineural hearing loss. There are a number of systemic barriers to creation of this new field of inner ear therapeutics. These include insufficient understanding of the particularity of different causes of hearing loss at the cellular and molecular level, lack of diagnostics of adequate sensitivity and specificity to discern these differences in vivo, a tendency for start-up biotech/pharma companies to prioritize competition over collaboration, and a drug development ecosystem that is really in the "pre-competitive" phase and a lack of infrastructure to develop, validate, gain regulatory approval, and successfully market an inner ear therapeutic. These issues will be discussed in this perspective article and a proposed remedy in the form of an inner ear therapeutics "moon shot" will be offered.

Supporting-cell vs. hair-cell survival in the human cochlea: Implications for regenerative therapies

Animal studies have shown that the supporting-cells surviving in the organ of Corti after cochlear insult can be transdifferentiated into hair cells as a treatment for sensorineural hearing loss. Clinical trials of small-molecule therapeutics have been undertaken, but little is known about how to predict the pattern and degree of supporting-cell survival based on audiogram, hearing loss etiology or any other metric obtainable pre-mortem. To address this, we systematically assessed supporting-cell and hair cell survival, as a function of cochlear location in 274 temporal bone cases from the archives at the Massachusetts Eye and Ear and compared the histopathology with the audiograms and hearing-loss etiologies. Results showed that supporting-cell survival was always significantly greater in the apical half than the basal half of the cochlea, that inner pillars were more robust than outer pillars or Deiters’ cells, and that total replacement of all supporting cells with a flat epithelium was rare outside of the extreme basal 20% of the cochlea. Supporting cell survival in the basal half of the cochlea was better correlated with the slope of the audiogram than with the mean high-frequency threshold per se: i.e. survival was better with flatter audiograms than with steeply down-sloping audiograms. Cochlear regions with extensive hair cell loss and exceptional supporting cell survival were most common in cases with hearing loss due to ototoxic drugs. Such cases also tended to have less pathology in other functionally critical structures, i.e. spiral ganglion neurons and the stria vascularis.

Precision medicine: Sensorineural hearing loss treatment

Precision medicine: Sensorineural hearing loss treatment Aarno Dietz, Professor of Otorhinolaryngology at Kuopio University Hospital, turns the spotlight on hospital precision medicine, focusing on the treatment of sensorineural hearing loss. Today, most medical treatments are designed for the average patient. This “one-size-fits-all-approach” may be effective for some patients but not others. Precision medicine refers to tailoring medical treatment to the individual characteristics of each patient, aiming to target the right treatments to the right patients at the right time. In general, a precision medicine approach does not mean unique treatments (e.g., drugs or medical devices) designed for each patient but rather the ability to classify individuals into subpopulations based on specific characteristics of the underlying disease or its response to a particular treatment. Advances in precision medicine have already led to new treatment strategies, e.g., in oncology, where tumour profiling is used to optimize adjuvant treatments, improving survival rates.

Amelioration of Sensorineural Hearing Loss through Regulation of Trpv1, Cacna1h, and Ngf Gene Expression by a Combination of Cuscutae Semen and Rehmanniae Radix Preparata

Sensorineural hearing loss (SNHL) is a common condition that results from the loss of function of hair cells, which are responsible for converting sound into electrical signals within the cochlea and auditory nerve. Despite the prevalence of SNHL, a universally effective treatment has yet to be approved. To address this absence, the present study aimed to investigate the potential therapeutic effects of TS, a combination of Cuscutae Semen and Rehmanniae Radix Preparata. To this end, both in vitro and in vivo experiments were performed to evaluate the efficacy of TS with respect to SNHL. The results showed that TS was able to protect against ototoxic neomycin-induced damage in both HEI-OC1 cells and otic hair cells in zebrafish. Furthermore, in images obtained using scanning electron microscopy (SEM), an increase in the number of kinocilia, which was prompted by the TS treatment, was observed in the zebrafish larvae. In a noise-induced hearing loss (NIHL) mouse model, TS improved hearing thresholds as determined by the auditory brainstem response (ABR) test. Additionally, TS was found to regulate several genes related to hearing loss, including Trpv1, Cacna1h, and Ngf, as determined by quantitative real-time polymerase chain reaction (RT-PCR) analysis. In conclusion, the findings of this study suggest that TS holds promise as a potential treatment for sensorineural hearing loss. Further research is necessary to confirm these results and evaluate the safety and efficacy of TS in a clinical setting.