Zebrafish neuromast sensory system: Is it an emerging target to assess environmental pollution impacts?

Environmental pollution poses risks to ecosystems. Among these risks, one finds neurotoxicity and damage to the lateral line structures of fish, such as the neuromast and its hair cells. Zebrafish (Danio rerio) is recommended as model species to be used in ecotoxicological studies and environmental biomonitoring programs aimed at assessing several biomarkers, such as ototoxicity. However, little is known about the history of and knowledge gaps on zebrafish ototoxicity. Thus, the aim of the current study is to review data available in the scientific literature about using zebrafish as animal model to assess neuromast toxicity. It must be done by analyzing the history and publication category, world production, experimental design, developmental stages, chemical classes, neuromasts and hair cell visualization methods, and zebrafish strains. Based on the results, number, survival and fluorescence intensity of neuromasts, and their hair cells, were the parameters oftentimes used to assess ototoxicity in zebrafish. The wild AB strain was the most used one, and it was followed by Tübingen and transgenic strains with GFP markers. DASPEI was the fluorescent dye most often applied as method to visualize neuromasts, and it was followed by Yo-Pro-1 and GFP transgenic lines. Antibiotics, antitumorals, metals, nanoparticles and plant extracts were the most frequent classes of chemicals used in the analyzed studies. Overall, pollutants can harm zebrafish's mechanosensory system, as well as affect their behavior and survival. Results have shown that zebrafish is a suitable model system to assess ototoxicity induced by environmental pollution.

Antioxidant Therapy as an Effective Strategy against Noise-Induced Hearing Loss: From Experimental Models to Clinic.

Cochlear redox unbalance is the main mechanism of damage involved in the pathogenesis of noise-induced-hearing loss. Indeed, the increased free radical production, in conjunction with a reduced efficacy of the endogenous antioxidant system, plays a key role in cochlear damage induced by noise exposure. For this reason, several studies focused on the possibility to use exogenous antioxidant to prevent or attenuate noise-induce injury. Thus, several antioxidant molecules, alone or in combination with other compounds, have been tested in both experimental and clinical settings. In our findings, we tested the protective effects of several antioxidant enzymes, spanning from organic compounds to natural compounds, such as nutraceuticals of polyphenols. In this review, we summarize and discuss the strengths and weaknesses of antioxidant supplementation focusing on polyphenols, Q-Ter, the soluble form of CoQ10, Vitamin E and N-acetil-cysteine, which showed great otoprotective effects in different animal models of noise induced hearing loss and which has been proposed in clinical trials.

Computational methodology for drug delivery to the inner ear using magnetic nanoparticle aggregates.

BACKGROUND AND OBJECTIVE: The main goal of the proposed study is to improve the efficiency of the ear treatment via targeted drug delivery to the inner ear, i.e. the cochlea. Although pharmacotherapy has been proposed as a solution to prevent damage or restore functionality to hair cells, the main challenge in such treatments is ensuring adequate drug delivery to the cells. To this end, we present a methodology for the evaluation of the magnetic forces needed to move magnetic particle nanorobots (abbreviated as MNP) and their aggregates through the cochlea round window membrane (RWM). METHODS: The FEM - Lagrangian-Eulerian approach (Abaqus software) was used to determine the specific parameters of movement of the nanoparticles crossing the RWM. This method results in a high consistency of FEM simulations and in-vivo experimental results in regards to the required magnetic force during the movement of spherical nanoparticles with a given viscosity ηave. Based on the analysis of the experimental studies found in subject literature, the sizes of the MNPs and their aggregates able to cross RWM with and without the application of magnetic force FM have been determined. RESULTS: The present work accounts for both the experimental and theoretical aspects of these investigations. Presented research confirms the definite usability of the Lagrange-Euler method for the precise determination of the required magnetic force value FM to control the accelerated motion of MNP aggregates of complex shapes through RWM. It is possible to determine the predominant parameters with a precision of less than 5% for single-layer aggregates and spatial aggregates crossing the RWM. It can be concluded that the MNPs and their aggregates should not be larger than 500-750 nm to cross the RWM with high velocities of penetration close to 800 nm/s for magnetic forces of hundreds 10-14 Newtons. CONCLUSIONS: The proposed Lagrangian-Eulerian approach is capable of accurately predicting the movement parameters of MNP aggregates of irregular shape that are close to the experimental test cases. The presented method can serve as a supplementary tool for the design of drug delivery systems to the inner ear using MNPs.

Pharmacologic treatments in preclinical tinnitus models with special focus on Ginkgo biloba leaf extract EGb 761®.

Tinnitus is defined as the perception of sound in the absence of external acoustic stimuli. Frequent comorbidities or associated factors are depression, anxiety, concentration problems, insomnia, resignation, helplessness, headache, bruxism, or social isolation, just to name a few. Although many therapeutic approaches have already been tested with varying success, there still is no cure available for tinnitus. The search for an effective treatment has been hampered by the fact that the mechanisms of tinnitus development are still not fully understood, although several models are available and discussed in this review. Our review will give a brief overview about preclinical models, presenting the heterogeneity of tinnitus sub-types depending on the different inner ear and brain structures involved in tinnitus etiology and pathogenesis. Based on these models we introduce the different target structures and transmitter systems implicated in tinnitus development and provide an extensive overview on preclinical drug-based therapeutic approaches that have been explored in various animal models. As the special extract from Ginkgo biloba leaves EGb 761® has been the most widely tested drug in both non-clinical tinnitus models as well as in clinical trials, a special focus will be given to EGb 761®. The efficacy of terpene lactones, flavone glycosides and proanthocyanidines with their distinct contribution to the overall efficacy profile of the multi-constituent drug EGb 761® will be discussed.

High-throughput screening on cochlear organoids identifies VEGFR-MEK-TGFB1 signaling promoting hair cell reprogramming.

Hair cell degeneration is a major cause of sensorineural hearing loss. Hair cells in mammalian cochlea do not spontaneously regenerate, posing a great challenge for restoration of hearing. Here, we establish a robust, high-throughput cochlear organoid platform that facilitates 3D expansion of cochlear progenitor cells and differentiation of hair cells in a temporally regulated manner. High-throughput screening of the FDA-approved drug library identified regorafenib, a VEGFR inhibitor, as a potent small molecule for hair cell differentiation. Regorafenib also promotes reprogramming and maturation of hair cells in both normal and neomycin-damaged cochlear explants. Mechanistically, inhibition of VEGFR suppresses TGFB1 expression via the MEK pathway and TGFB1 downregulation directly mediates the effect of regorafenib on hair cell reprogramming. Our study not only demonstrates the power of a cochlear organoid platform in high-throughput analyses of hair cell physiology but also highlights VEGFR-MEK-TGFB1 signaling crosstalk as a potential target for hair cell regeneration and hearing restoration.

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice.

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Children with Auditory Brainstem Implant: How Do They Perform in Motor and Language Skills?

BACKGROUND: Young children are able to explore new objects and practice language through the acquisition of motor skills that lead to their overall development. Congenital hearing loss and total vestibular loss may contribute to the delay in speech and motor skill development. OBJECTIVES: To investigate the relationship between motor development performance, speech perception, and language performance in children with auditory brainstem implant (ABI). METHOD: Ten children, aged 4-17 years (mean age 9.76 ± 4.03), fitted with unilateral ABI for at least 2 years due to the presence of labyrinthine aplasia and rudimentary otocyst at least 1 side were included in the study. Several standardized tests, such as Bruininks-Oseretsky Motor Proficiency Test-2 (BOT-2), Children's Auditory Perception Test Battery, Meaningful Auditory Integration Scale (MAIS), and Test of Early Language Development-3, were performed to evaluate their skills of fine motor control, balance, manual dexterity, language, and auditory perception. RESULTS: A significant correlation was established between the BOT-2 manual dexterity and MAIS scores (r = 0.827, p < 0.05) and between the manual dexterity and language skills (for expressive language, r = 0.762, p < 0.05; for receptive language, r = 0.650, p < 0.05). Some of the BOT-2 balance tasks, such as standing on 1 leg on a line with eyes closed, standing on 1 leg on a balance beam with eyes open, standing heel-to-toe on a balance beam, and walking forward heel-to-toe on a line, showed a strong correlation with their receptive and expressive language performance (p < 0.05). CONCLUSION: The current study has indicated that significantly poor manual and balance performances are associated with poor speech perception and language skills in children with ABI. The authors recommend performing a vestibular assessment before and after ABI surgery and the use of a holistic rehabilitation approach, including auditory and vestibular rehabilitation, to support development of the children with ABI.

Clinical efficacy of hyperbaric oxygen therapy on idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as unexplained hearing loss of at least 30 decibels (dB) occurring within 72 hours over at least three contiguous frequencies. ISSHL is common and has a significant effect on quality of life. Hyperbaric oxygen (HBO2) therapy is a medical treatment method that aims to increase the level of dissolved oxygen in the tissues. Correcting perilymph hypoxia is the goal of HBO2 therapy for ISSHL. In recent years, HBO2 therapy has been increasingly involved in the treatment of ISSHL. The medical records of 135 patients who had received HBO2 therapy for ISSHL were reviewed. Demographic properties of patients, severity of hearing loss, delay until HBO2 therapy, number of HBO2 therapy sessions and outcomes were evaluated. Findings of the present study are similar to most of previous studies that demonstrate that HBO2 therapy as adjunctive treatment results in an improvement of hearing. Early treatment is important for ISSHL, and HBO2 therapy is recommended in the early period, particularly within 14 days of onset.

Inner ear organoids: new tools to understand neurosensory cell development, degeneration and regeneration.

The development of therapeutic interventions for hearing loss requires fundamental knowledge about the signaling pathways controlling tissue development as well as the establishment of human cell-based assays to validate therapeutic strategies ex vivo Recent advances in the field of stem cell biology and organoid culture systems allow the expansion and differentiation of tissue-specific progenitors and pluripotent stem cells in vitro into functional hair cells and otic-like neurons. We discuss how inner ear organoids have been developed and how they offer for the first time the opportunity to validate drug-based therapies, gene-targeting approaches and cell replacement strategies.

Different prognoses in patients with profound sudden sensorineural hearing loss.

Background: Inner ear hemorrhage is increasingly recognized as a cochlear lesion that can cause profound sudden sensorineural hearing loss (SSNHL). Objectives: To investigate changes of cochlear and vestibular function and to compare therapeutic recovery from profound SSNHL induced by different etiologies. Material and methods: Eighty patients with profound SSNHL (≥90 dB) were divided into an inner ear hemorrhage group and a non-inner ear hemorrhage group by MRI. Statistical analysis was performed to compare the therapeutic effects from vertigo and hearing loss and the outcomes of follow-up in the two groups. Results: There were significant differences between the two groups in terms of the overall 14-day therapeutic response rate (20 vs. 48%), the incidence of imbalance (26.7 vs. 6%), the incidence of semicircular canal dysfunction on the affected side (60 vs. 20%), the incidence of abnormal C-VEMP and O-VEMP on the affected side (63.3 vs. 38%; and 60 vs. 30%, respectively), the average hearing threshold (74.2 ± 10.7 vs. 53.6 ± 11.4 dB), and the word recognition score (65.5 ± 21.7 vs. 83.5 ± 24.5%) at a 12-month follow-up. Conclusions and significance: A higher percentage of patients with profound SSNHL induced by inner ear hemorrhage were associated with vertigo and had a poor prognosis.

Ginkgo biloba extract EGb 761® alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials.

BACKGROUND: Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, Ginkgo biloba extract EGb 761® was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761® at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. METHODS: Randomized, placebo-controlled clinical trials of G. biloba extract EGb 761® identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. RESULTS: Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761® was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for tinnitus (p = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness (p = 0.03). CONCLUSION: Our findings support the notion that EGb 761® is also effective in alleviating concomitant neurosensory symptoms in patients with dementia.

The Development of a Nano-based Approach to Alleviate Cisplatin-Induced Ototoxicity.

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles' ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

An update on drug design strategies to prevent acquired sensorineural hearing loss.

INTRODUCTION: Acute sensorineural hearing loss is a dramatic event for the patient. Different pathologies might result in acute sensorineural hearing loss, such as sudden hearing loss, exposure to medications/drugs or loud sound. Current therapeutic approaches include steroids and hyperbaric oxygen in addition to other methods. Research activities of the past have shed light on the molecular mechanisms involved in damage to hair cells, the synapses at the hair cell spiral ganglion junction and the stria vascularis. Molecular events and signaling pathways which underlie damage to these structures have been discovered. Areas covered: This paper summarizes current research efforts involved in investigating the molecular mechanisms involved in acute sensorineural hearing loss. Expert opinion: While progress has been made in unraveling basic mechanisms involved in acute sensorineural hearing loss, it is difficult to translate basic concepts to the clinic. There are often conflicting data in animal and human studies on the effect of a given intervention. There is also a lack of high quality clinical trials (double blind, placebo controlled and high powered). However, this author is confident that research efforts will pay out and that some of these efforts will translate into new therapeutic options for patients with acute hearing loss.

Retroauricular Approach for Targeted Cochlear Therapy Experiments in Wistar Albino Rats.

BACKGROUND: As the idea of stem cell technology in the treatment of sensorial hearing loss has emerged over the past decades, the need for in vivo models for related experiments has become explicit. One of the most common experimental models for inner ear stem cell delivery experiments is the Wistar albino rat. AIMS: To investigate the surgical anatomy of the temporal bone of the Wistar albino rat with respect to the dissection steps, operative techniques and potential pitfalls of surgery. STUDY DESIGN: Animal experimentation. METHODS: Adult Wistar albino rats were operated on via the retroauricular approach under an operation microscope. The anatomy of the temporal bone, the surgical route to the temporal bulla and the inner ear were investigated. Technical details of surgical steps, complications and potential pitfalls during the surgery were noted. RESULTS: The study group consisted of 40 adult Wistar albino rats. The mean times to reach the bulla and to achieve cochleostomy were 4.3 (2-13 min) and 7.5 min (3.5-22 min), respectively. The mean width of the facial nerve was 0.84 mm (0.42-1.25 mm). The stapedial artery lay nearly perpendicular to the course of the facial nerve (88-93 °C). There were three major complications: two large cochleostomies and one massive bleed from the stapedial artery. CONCLUSION: The facial nerve was the key anatomical landmark in locating the bulla. By retrograde tracing of the facial nerve, it was possible to find the bulla ventral (inferior) to the main trunk. The facial nerve trunk was the upper limit when drilling the bulla. By dissecting the main trunk of the facial nerve and retracting cranially, a large drilling space could be achieved. Our results suggest that the retroauricular approach is an effective, feasible route for inner ear drug delivery experiments in Wistar albino rats.

Hyperbaric oxygen therapy in the treatment of sudden sensorineural hearing loss: a retrospective analysis of outcomes.

OBJECTIVE: To analyse predictive factors affecting outcome after treatment with hyperbaric oxygen (HBOT) in patients with idiopathic sudden sensorineural hearing loss (ISSHL). METHODS: This is a retrospective audit of outcome in 77 consecutive patients referred for consideration of HBOT for ISSHL for either adjunctive treatment or after failure of steroid therapy. The hearing measured from the pre- and post-HBOT pure-tone audiogram (PTA4) at four frequencies; 500 Hz, 1 kHz, 2 kHz and 4 kHz, was averaged and compared. The PTA4 score was classified into three groups: complete improvement (≤ 25 dB residual hearing loss); moderate improvement (11-50 dB gain) and no improvement (≤ 11dB gain). Data were also analysed using mean residual loss on completion as the outcome measure. RESULTS: Seventy-six patients underwent 1,029 HBOT sessions. Twenty five of 78 ears (33%) had complete resolution of deafness after HBOT. A further 31 (40%) had a significant improvement in PTA4. Delay (〉 28 days) and older age were associated with worse outcomes in PTA4 improvement. Those with less severe hearing loss and short delay (〈 15 days) had the best outcome (mean residual loss 28 dB). Eight of nine patients who were delayed 〉 28 days had no improvement in PTA4. CONCLUSIONS: Fifty-six of 76 (74%) patients had complete (25) or moderate (31) improvement in hearing loss after HBOT. Short delay to HBOT, a severer degree of hearing loss and younger age were the best predictive factors of improved PTA4. Outcome was poor if treatment was delayed over 28 days. Well-designed randomised controlled trials are needed to clarify the role of HBOT and steroids.

Neuroplastin Isoform Np55 Is Expressed in the Stereocilia of Outer Hair Cells and Required for Normal Outer Hair Cell Function.

UNLABELLED: Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanontransduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function. SIGNIFICANCE STATEMENT: Amplification of input sound signals, which is needed for the auditory sense organ to detect sounds over a wide intensity range, depends on mechanical coupling of outer hair cells to the tectorial membrane. The current study shows that neuroplastin, a member of the Ig superfamily, which has previously been linked to the regulation of synaptic plasticity, is critical to maintain a stable mechanical link of outer hair cells with the tectorial membrane. In vivo recordings demonstrate that neuroplastin is essential for sound amplification and that mutation in neuroplastin leads to auditory impairment in mice.

Vestibular evoked myogenic potentials in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease with unknown etiology. Although sacroiliac joint involvement is the classic sign along with the formed immune mediators, it may result in immune-mediated inner ear disease and may cause damage to the audiovestibular system. Vestibular evoked myogenic potentials (VEMP) is a clinical reflex test used in the diagnosis of vestibular diseases and is performed by recording and evaluating the muscle potentials resulting from the stimulation of the vestibular system with different stimuli. The aim of this study is to evaluate the cervical VEMP test results in AS patients without vestibular symptoms. Thirty-three patients with AS and a control group of 30 healthy volunteers with similar demographic characteristics were evaluated in the study. VEMP wave latency, P13-N23 wave amplitude, and VEMP asymmetry ratio (VAR) values were compared between the groups. The relationship between clinical and laboratory findings of the AS patients and VEMP data were also investigated. Compared with healthy people, this study shows the response rate of patients with ankylosing spondylitis was reduced in the VEMP test, and P13-N23 wave amplitude showed a decrease in AS patients who had VEMP response (p < 0.001). There was no correlation between the clinical and laboratory findings and VEMP findings in patients with ankylosing spondylitis. The data obtained from this study suggest that AS may lead to decreased sensitivity of the vestibular system.

Directional Hearing and Sound Source Localization in Fishes.

Evidence suggests that the capacity for sound source localization is common to mammals, birds, reptiles, and amphibians, but surprisingly it is not known whether fish locate sound sources in the same manner (e.g., combining binaural and monaural cues) or what computational strategies they use for successful source localization. Directional hearing and sound source localization in fishes continues to be important topics in neuroethology and in the hearing sciences, but the empirical and theoretical work on these topics have been contradictory and obscure for decades. This chapter reviews the previous behavioral work on directional hearing and sound source localization in fishes including the most recent experiments on sound source localization by the plainfin midshipman fish (Porichthys notatus), which has proven to be an exceptional species for fish studies of sound localization. In addition, the theoretical models of directional hearing and sound source localization for fishes are reviewed including a new model that uses a time-averaged intensity approach for source localization that has wide applicability with regard to source type, acoustic environment, and time waveform.

Perspectives for the treatment of sensorineural hearing loss by cellular regeneration of the inner ear.

Sensorineural hearing loss is a caused by the loss of the cochlear hair cells with the consequent deafferentation of spiral ganglion neurons. Humans do not show endogenous cellular regeneration in the inner ear and there is no exogenous therapy that allows the replacement of the damaged hair cells. Currently, treatment is based on the use of hearing aids and cochlear implants that present different outcomes, some difficulties in auditory discrimination and a limited useful life. More advanced technology is hindered by the functional capacity of the remaining spiral ganglion neurons. The latest advances with stem cell therapy and cellular reprogramming have developed several possibilities to induce endogenous regeneration or stem cell transplantation to replace damaged inner ear hair cells and restore hearing function. With further knowledge of the cellular and molecular biology of the inner ear and its embryonic development, it will be possible to use induced stem cells as in vitro models of disease and as replacement cellular therapy. Investigation in this area is focused on generating cellular therapy with clinical use for the treatment of profound sensorineural hearing loss.

Does the addition of a second daily session of hyperbaric oxygen therapy to intratympanic steroid influence the outcomes of sudden hearing loss?

The aim of this study is to investigate whether, in addition to intratympanic steroid therapy, additional hyperbaric oxygen therapy (HBOT) sessions per day (twice a day for 5 days) is more useful than one session per day for 10 days in patients affected by severe and profound idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 55 patients affected by unilateral severe and profound ISSNHL were recruited. Two protocols were adopted. In the first, 27 patients (13 with profound and 14 with severe hearing loss) underwent one session of HBOT per day for 10 days, 6 days a week. An HBOT session comprised a period of 14 minutes air compression followed by 90 min at 2.4 atm absolute (ATA) followed by a decompression period of 15 min in oxygen. Patients breathed 100% oxygen through an appropriate mask checked for leaks. Patients were given 0.4 ml of 62.5 mg/ml of intratympanic prednisolone during the first three days of the protocol. In the second protocol, 28 patients (10 with profound and 18 with severe hearing loss) received 10 sessions of HBOT, twice a day for five days, 2.4 ATA 90 min 100% oxygen. The intratympanic injections of prednisolone were given between the two sessions of HBOT during the first three days of the protocol. Since there were no significant differences in hearing outcomes between the two protocols, the present study shows that the protocol of two sessions of HBOT per day is a valid treatment and equally effective as the one HBOT session per day, but with shorter treatment time.