Intracochlear Trauma and Local Ossification Patterns Differ Between Straight and Precurved Cochlear Implant Electrodes.

HYPOTHESIS: Trauma to the osseous spiral lamina (OSL) or spiral ligament (SL) during cochlear implant (CI) insertion segregates with electrode type and induces localized intracochlear ossification and fibrosis. BACKGROUND: The goal of atraumatic CI insertion is to preserve intracochlear structures, limit reactive intracochlear tissue formation, and preserve residual hearing. Previous qualitative studies hypothesized a localized effect of trauma on intracochlear tissue formation; however, quantitative studies failed to confirm this. METHODS: Insertional trauma beyond the immediate insertion site was histologically assessed in 21 human temporal bones with a CI. Three-dimensional reconstructions were generated and virtually resectioned perpendicular to the cochlear spiral at high resolution. The cochlear volume occupied by ossification or fibrosis was determined at the midpoint of the trauma and compared with regions proximal and distal to this point. RESULTS: Seven cases, all implanted with precurved electrodes, showed an OSL fracture beyond the immediate insertion site. Significantly more intracochlear ossification was observed at the midpoint of the OSL fracture, compared with the -26 to -18 degrees proximal and 28 to 56 degrees distal to the center. No such pattern was observed for fibrosis. In the 12 cases with a perforation of the SL (9 straight and 3 precurved electrodes), no localized pattern of ossification or fibrosis was observed around these perforations. CONCLUSION: OSL fractures were observed exclusively with precurved electrodes in this study and may serve as a nidus for localized intracochlear ossification. Perforation of the SL, in contrast, predominantly occurred with straight electrodes and was not associated with localized ossification.

Intraoperative Measured Electrocochleography and Fluoroscopy Video to Detect Cochlea Trauma.

HYPOTHESIS: Gross electrode movements detected with intraoperative, real-time X-ray fluoroscopy will correlate with fluctuations in cochlear output, as measured with intraoperative electrocochleography (ECochG). BACKGROUND: Indications for cochlear implantation (CI) are expanding to include patients with residual hearing; however, implant recipients often lose residual hearing after CI. The objective of this study was to identify probable traumatic events during implantation by combining electrophysiological monitoring of cochlear function with simultaneous X-ray monitoring. The surgical timing of these apparently traumatic events was then investigated. METHODS: For 19 adult patients (21 surgeries, 2 bilateral), the ECochG responses were measured during implantation of a cochlear nucleus slim modiolar electrode (CI532/CI632, Cochlear Ltd Australia Nucleus slim modiolar). Simultaneous fluoroscopy was performed, as well as a postoperative cone-beam computed tomography (CT) scan. For all patients, pre- and postoperative audiograms were recorded up to 1 year after surgery to record the loss of residual hearing. RESULTS: Electrode insertions for 21 surgeries were successfully monitored. A drop in ECochG response was significantly correlated with reduced hearing preservation compared with patients with preserved responses throughout. Drops in the ECochG response were measured to occur during insertion, because of movement of the array after insertion was complete, including while sealing of the electrode array at the round window or coiling of the array lead within the mastoid cavity. In some patients, a reduction in cochlear output, resulting in poor ECochG response, was inferred to occur before the beginning of implantation. CONCLUSION: The combination of perioperative ECochG measurements, microscope video, fluoroscopy, and postoperative CT scan may inform on what causes the loss of residual hearing after implantation. These findings will be used to improve the surgical procedure in future.

Mild therapeutic hypothermia protects against inflammatory and proapoptotic processes in the rat model of cochlear implant trauma.

OBJECTIVE: Mild therapeutic hypothermia (MTH) has been demonstrated to prevent residual hearing loss from surgical trauma associated with cochlear implant (CI) insertion. Here, we aimed to characterize the mechanisms of MTH-induced hearing preservation in CI in a well-established preclinical rodent model. APPROACH: Rats were divided into four experimental conditions: MTH-treated and implanted cochleae, cochleae implanted under normothermic conditions, MTH only cochleae and un-operated cochleae (controls). Auditory brainstem responses (ABRs) were recorded at different time points (up to 84 days) to confirm long-term protection and safety of MTH locally applied to the cochlea for 20 min before and after implantation. Transcriptome sequencing profiling was performed on cochleae harvested 24 h post CI and MTH treatment to investigate the potential beneficial effects and underlying active gene expression pathways targeted by the temperature management. RESULTS: MTH treatment preserved residual hearing up to 3 months following CI when compared to the normothermic CI group. In addition, MTH applied locally to the cochleae using our surgical approach was safe and did not affect hearing in the long-term. Results of RNA sequencing analysis highlight positive modulation of signaling pathways and gene expression associated with an activation of cellular inflammatory and immune responses against the mechanical damage caused by electrode insertion. SIGNIFICANCE: These data suggest that multiple and possibly independent molecular pathways play a role in the protection of residual hearing provided by MTH against the trauma of cochlear implantation.

An optically-guided cochlear implant sheath for real-time monitoring of electrode insertion into the human cochlea.

In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This novel device enables the surgeon to accurately detect and identify the cochlear walls ahead and to adjust the insertion trajectory, avoiding collision and trauma. The functionality of this prototype has been demonstrated in a series of insertion experiments, conducted by experienced cochlear implant surgeons on fresh-frozen human cadaveric cochleae.

Cochlear implant explantation: An in vitro model to evaluate electrode explant force and trauma.

OBJECTIVES: Removal of a cochlear implant and its intracochlear electrode array is sometimes necessary, potentially causing cochlear explant trauma. Explantation typically occurs years post-implantation by which time reactive tissue has formed around the electrode. We aimed to create an in-vitro electrode explant model to examine explant forces and intracochlear trauma across multiple electrode types and insertion depths. STUDY DESIGN: An in-vitro model using gel to represent tissue surrounding the electrode was developed. Pre-curved electrodes and straight electrodes at different insertion depths (20mm, 25mm, 28mm) were explanted from the model. During explantation, explant force was measured, and high-definition videos were recorded to capture electrode exit path and gel disruption. RESULTS: Explant force patterns varied based on electrode position in the scala tympani. Explant forces did not correlate with gel disruption, which represented explant trauma. The least gel disruption occurred with pre-curved electrodes and the under-inserted straight electrode. The greatest disruption occurred with the overly inserted straight electrode. CONCLUSION: An in-vitro model using gel to mimic tissue surrounding the electrode may provide insights into potential electrode explant trauma. Explant force did not correlate with explant trauma in our model. Pre-curved electrodes and shallower insertion depth of a straight electrode resulted in the least amount of explant trauma.

Ultrasonic bone removal from the ossicular chain affects cochlear structure and function.

INTRODUCTION: Ultrasonic bone removal devices (UBD) are capable of cutting through bony tissue without injury to adjacent soft tissue. The feasibility and safety of using this technology for removal of bone from an intact ossicular chain (as might be required for otosclerosis or congenital fixation) was investigated in an animal model. METHODS: This was a prospective animal study conducted on seven anesthetised adult chinchillas. An UBD was used to remove bone from the malleus head in situ. Pre and post-operative distortion product otoacoustic emission (DPOAE) levels and auditory brainstem response (ABR) thresholds were recorded. Scanning electron microscopy (SEM) was used to assess cochlear haircell integrity. RESULTS: Precise removal of a small quantity of bone from the malleus head was achieved by a 30s application of UBD without disruption of the ossicular chain or tympanic membrane. DPOAEs became undetectable after the intervention with signal-to-noise ratios (SNR) < 5 dB SPL in all ears. Furthermore, ABR thresholds were elevated > 85 dB SPL in 13 ears. SEM showed significant disruption of structural integrity of the organ of Corti, specifically loss and damage of outer haircells. CONCLUSIONS: Although UBD can be used to reshape an ossicle without middle ear injury, prolonged contact with the ossicular chain can cause structural and functional injury to the cochlea. Extensive cochlea pathology was found, but we did not investigate for recovery from any temporary threshold shift. In the authors' opinion, further study should be undertaken before consideration is given to use of the device for release of ossicular fixation.

Insertion trauma of a new cochlear implant electrode: evaluated by histology in fresh human temporal bone specimens.

BACKGROUND: Combining acoustic and electrical stimulation has been successfully used in patients with low-frequency residual hearing. Electrode insertion trauma, such as electrode translocation could result in loss of residual hearing. OBJECTIVES: The aim of the study is to evaluate the LCI-20PI electrode array insertion trauma to the intra-cochlear structures in fresh human temporal bone specimens. MATERIALS AND METHODS: The LCI-20PI electrode arrays were inserted into scalae tympani through round window membrane in 10 cochleae from ten fresh human cadavers. The intracochlear trauma was evaluated histologically by a scale of 0-4: 0 - no observable trauma, 1 - elevation of basilar membrane, 2 - rupture of basilar membrane or spiral ligament, 3-dislocation into scala vestibuli and 4 - fracture of modiolus or osseous spiral lamina. The insertion depth was measured by radiography. RESULTS: Histological results revealed no observable trauma in seven specimens; basal membrane elevation and rupture in two specimens; the electrode array misled into scala vestibuli in one specimen. The insertion depth varied from 228° to 288°. CONCLUSIONS AND SIGNIFICANCE: The insertion of the LCI-20PI electrode arrays caused no trauma in the majority of the fresh temporal bone specimens. No translocation of the electrode arrays from the scala tympani to the scala vestibuli was observed.

Neuroprotectin D1 Attenuates Blast Overpressure Induced Reactive Microglial Cells in the Cochlea.

OBJECTIVE/HYPOTHESIS: We examined a neuroinflammatory response associated with glial activation in the cochlea exposed to blast overpressure and evaluated the potential therapeutic efficacy of specialized pro-resolving mediators such as neuroprotectin D1, NPD1; (10R, 17S-dihydroxy-4Z, 7Z, 11E, 13E, 15Z, 19Z-docosahexaenoic acid) in a rodent blast-induced auditory injury model. STUDY DESIGN: Animal Research. METHODS: A compressed-air driven shock tube was used to expose anesthetized adult male Long-Evan rats to shock waves simulating an open-field blast exposure. Approximately 30 minutes after blast exposure, rats were treated with NPD1 (100 ng/kg body wt.) or vehicle delivered intravenously via tail vein injection. Rats were then euthanized 48 hours after blast exposure. Unexposed rats were included as controls. Tissue sections containing both middle and inner ear were prepared with hematoxylin-eosin staining to elucidate histopathological changes associated with blast exposure. Cochlear tissues were evaluated for relative expression of ionized calcium-binding adaptor 1 (Iba1), as an indicator of microglial activation by immunohistochemistry and western blot analyses. RESULTS: Our animal model resulted in an acute injury mechanism manifested by damage to the tympanic membrane, hemorrhage, infiltration of inflammatory cells, and increased expression of Iba1 protein. Moreover, therapeutic intervention with NPD1 significantly reduced Iba1 expression in the cochlea, suggesting a reduction of a neuroinflammatory response caused by blast overpressure. CONCLUSIONS: Blast overpressure resulted in an increased expression of proteins involved in gliosis within the auditory system, which were reduced by NPD1. Treatment of NPD1 suggests an effective strategy to reduce or halt auditory microglial cell activation due to primary blast exposure. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E2018-E2025, 2021.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

The immune response after noise damage in the cochlea is characterized by a heterogeneous mix of adaptive and innate immune cells.

Cells of the immune system are present in the adult cochlea and respond to damage caused by noise exposure. However, the types of immune cells involved and their locations within the cochlea are unclear. We used flow cytometry and immunostaining to reveal the heterogeneity of the immune cells in the cochlea and validated the presence of immune cell gene expression by analyzing existing single-cell RNA-sequencing (scRNAseq) data. We demonstrate that cell types of both the innate and adaptive immune system are present in the cochlea. In response to noise damage, immune cells increase in number. B, T, NK, and myeloid cells (macrophages and neutrophils) are the predominant immune cells present. Interestingly, immune cells appear to respond to noise damage by infiltrating the organ of Corti. Our studies highlight the need to further understand the role of these immune cells within the cochlea after noise exposure.

The Role of Cognition in Common Measures of Peripheral Synaptopathy and Hidden Hearing Loss.

Purpose The aim of this study was to quantify the portion of variance in several measures suggested to be indicative of peripheral noise-induced cochlear synaptopathy and hidden hearing disorder that can be attributed to individual cognitive capacity. Method Regression and relative importance analysis was used to model several behavioral and physiological measures of hearing in 32 adults ranging in age from 20 to 74 years. Predictors for the model were hearing sensitivity and performance on a number of cognitive tasks. Results There was a significant influence of cognitive capacity on several measures of cochlear synaptopathy and hidden hearing disorder. These measures include frequency modulation detection threshold, time-compressed word recognition in quiet and reverberation, and the strength of the frequency-following response of the speech-evoked auditory brainstem response. Conclusions Measures of hearing that involve temporal processing are significantly influenced by cognitive abilities, specifically, short-term and working memory capacity, executive function, and attention. Research using measures of temporal processing to diagnose peripheral disorders, such as noise-induced synaptopathy, need to consider cognitive influence even in a young, healthy population.

What is noise-induced hearing loss?

Noise-induced hearing loss is sensory deafness caused by long-term exposure of the auditory system to a noisy environment. Auditory fatigue is an early symptom of noise-induced hearing loss, and hearing can gradually recover after people leave a noisy environment. However, if people remain in a noisy environment for a prolonged period of time, their hearing will be permanently impaired. Societal changes mean that people are more likely to be exposed to noise. The hearing loss and tinnitus caused by noise seriously affect people's quality of life and lead to huge economic loss. The pathogenesis of noise-induced hearing loss is complex. Various theories try to explain this, such as the oxidative stress theory, but none perfectly explains the occurrence of noise-induced hearing loss. There is no treatment which can completely reverse the damage. More research is required to explore the pathogenesis and to better guide clinical practice. Preventative strategies, such as educating the public about hearing health, should be adopted to reduce the harm of noise-induced hearing loss.

Inhibition of the Adenosine A2A Receptor Mitigates Excitotoxic Injury in Organotypic Tissue Cultures of the Rat Cochlea.

The primary loss of cochlear glutamatergic afferent nerve synapses due to noise or ageing (cochlear neuropathy) often presents as difficulties in speech discrimination in noisy conditions (hidden hearing loss (HHL)). Currently, there is no treatment for this condition. Our previous studies in mice with genetic deletion of the adenosine A2A receptor (A2AR) have demonstrated better preservation of cochlear afferent synapses and spiral ganglion neurons after noise exposure compared to wildtype mice. This has informed our current targeted approach to cochlear neuroprotection based on pharmacological inhibition of the A2AR. Here, we have used organotypic tissue culture of the Wistar rat cochlea at postnatal day 6 (P6) to model excitotoxic injury induced by N-methyl-d-aspartate (NMDA)/kainic acid (NK) treatment for 2 h. The excitotoxic injury was characterised by a reduction in the density of neural processes immediately after NK treatment and loss of afferent synapses in the presence of intact sensory hair cells. The administration of istradefylline (a clinically approved A2AR antagonist) reduced deafferentation of inner hair cells and improved the survival of afferent synapses after excitotoxic injury. This study thus provides evidence that A2AR inhibition promotes cochlear recovery from excitotoxic injury, and may have implications for the treatment of cochlear neuropathy and prevention of HHL.

Hidden hearing deficits in military service members with persistent post concussive symptoms.

INTRODUCTION: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms. METHODS: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50. RESULTS: 37/69 mTBI participants had measurable hearing loss, while another 20%-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls. CONCLUSION: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.

[Models of tinnitus development : From cochlea to cortex]. / Modelle der Tinnitusentstehung : Von der Cochlea zum Kortex.

The development of subjective tinnitus is still not mechanistically understood and existing models are controversially discussed. In this overview, the authors discuss three of the main models, all of which propose damage to the cochlea as the initial step in tinnitus development. Based on these models, a possible manifestation of tinnitus-related neuronal activity at the perceptually relevant level of the auditory pathway, the auditory cortex, is presented. Furthermore, it is demonstrated that one of the models offers a new view on the phenomenon, which could potentially help patients to better cope with their condition.

Traumatic Injury of the Petrous Part of the Temporal Bone: Keys for Reporting a Complex Diagnosis. / Patología traumática de peñascos, un diagnóstico complejo. Claves para el informe.

Fractures of the petrous part of the temporal bone are a common lesion of the base of the skull; most of these fractures result from high-energy trauma. In patients with multiple trauma, these injuries can be detected on CT scans of the head and neck, where the direct and indirect signs are usually sufficient to establish the diagnosis. It is important to these fractures because the temporal bone has critical structures and the complexity of this region increases the risk of error unless special care is taken. This article reviews the key anatomical points, the systematization of the imaging findings, and the classifications used for temporal bone fracture. We emphasize the usefulness of identifying and describing the findings in relation to important structures in this region, of looking for unseen fractures suspected through indirect signs, and of identifying anatomical structures that can simulate fractures. We point out that the classical classifications of these fractures are less useful, although they continue to be used for treatment decisions.

Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation.

The hybrid or electric-acoustic stimulation cochlear implant is indicated in patients with a residual hearing at low frequencies. It provides electric and acoustic stimulation for compensating for high- and low-frequency sounds, respectively. However, the implantation procedure damages the cochlea, resulting in loss of the residual-hearing and diminished effects of the acoustic-hearing in several patients. To prevent hearing loss after implantation, corticosteroids have been used clinically although their effects are limited. As an alternative to corticosteroids, insulin-like growth factor 1 (IGF1) has shown potent effects in various types of cochlear injury. In this study, the effects of IGF1 on hearing preservation were examined after cochlear implantation to a normal-hearing guinea pig model. The electrode was inserted in an atraumatic way through the round window membrane of guinea pigs with the application of a gelatin-sponge soaked with IGF1 or saline. The auditory brainstem response (ABR) was recorded pre-operatively, immediately after cochlear implantation, and 7, 14, 28, and 56 days after electrode insertion. In comparison to the control group, the IGF1-treated group showed better hearing preservation at low frequencies, 7 days after surgery. IGF1 application was effective at low frequencies (2 and 4 kHz) throughout the period of examination. Histological studies revealed that outer hair cell numbers, in the IGF1-treated group, were maintained in the cochlear region responsible for low-frequency hearing (upper midbasal turn) and that there was less fibrous tissue formation around the electrode. Both the outer hair cell counts and the extent of fibrosis significantly correlated with the ABR threshold shifts at low frequencies. These results indicate that IGF1 might attenuate loss of low-frequency hearing after cochlear implantation, suggesting its possible clinical use in soft surgeries involving cochlear implants with electric-acoustic stimulation for hearing preservation.

Intracochlear pressure in response to high intensity, low frequency sounds in chinchilla.

Exposure to high intensity (blast) sounds can result in both conductive and sensorineural damage to hearing. This includes rupture of the tympanic membrane and dislocation of the middle ear ossicles, as well as damage to the inner and outer hair cells in the cochlea. A clearer understanding of how the hearing system responds to blast could help us better prevent auditory trauma, and support those who have been exposed to such sounds. Chinchillas are often used in studies of hearing due to the similarity between the chinchilla and human audiograms. The suitability of their use in research on auditory trauma from blast noise will depend on the extent to which cochlear pressures generated in chinchillas compare to those in humans. In order to gain a more detailed understanding of the response of the ear to high intensity sounds, a custom built sound concentrating horn was used to expose chinchilla cadaveric ears to a series of single frequency tones between 10 and 1280 Hz, with varying intensities from 90 to 194 dB SPL while intracochlear pressures were measured simultaneously in the scala vestibuli and scala tympani. These results were then compared to similar, previously published data from human cadavers. In both human and chinchillas, intracochlear pressures increased with applied sound pressure up to about 120 dB SPL, but began to saturate at higher intensities. The exact saturation point and the saturation pressures showed a strong frequency dependence. Intracochlear pressure magnitudes in chinchillas show some similarities with those measured in humans, but also significant differences, particularly at very high intensity levels such as those found in a blast. These differences should be taken into account when conducting blast studies in chinchillas.

Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111).

There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea.