Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils.

AIM: Auditory neuropathy (AN) is a hearing disorder characterized by abnormal auditory nerve function with preservation of normal cochlear hair cells. This study was designed to investigate whether treatment with molecular hydrogen (H(2)), which can remedy damage in various organs via reducing oxidative stress, inflammation and apoptosis, is beneficial to ouabain-induced AN in gerbils. METHODS: AN model was made by local application of ouabain (1 mmol/L, 20 mL) to the round window membrane in male Mongolian gerbils. H(2) treatment was given twice by exposing the animals to H(2) (1%, 2%, and 4%) for 60 min at 1 h and 6 h after ouabain application. Before and 7 d after ouabain application, the hearing status of the animals was evaluated using the auditory brainstem response (ABR) approach, the hear cell function was evaluated with distortion product otoacoustic emissions (DPOAE). Seven days after ouabain application, the changes in the cochleae, especially the spiral ganglion neurons (SGNs), were morphologically studied. TUNEL staining and immunofluorescent staining for activated caspase-3 were used to assess the apoptosis of SGNs. RESULTS: Treatment with H(2) (2% and 4%) markedly attenuated the click and tone burst-evoked ABR threshold shift at 4, 8, and 16 kHz in ouabain-exposed animals. Neither local ouabain application, nor H(2) treatment changed the amplitude of DPOAE at 4, 8, and 16 kHz. Morphological study showed that treatment with H(2) (2%) significantly alleviated SGN damage and attenuated the loss of SGN density for each turn of cochlea in ouabain-exposed animals. Furthermore, ouabain caused significantly higher numbers of apoptotic SGNs in the cochlea, which was significantly attenuated by the H(2) treatment. However, ouabain did not change the morphology of cochlear hair cells. CONCLUSION: The results demonstrate that H(2) treatment is beneficial to ouabain-induced AN via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.

Transplantation of neural differentiated human mesenchymal stem cells into the cochlea of an auditory-neuropathy guinea pig model.

The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We established the auditory neuropathy guinea pig model using 1 mM ouabain application to the round window niche. After application of ouabain to the round window niche, degeneration of most spiral ganglion neurons (SGNs) without the loss of hair cells within the organ of Corti and increasing the auditory brain responses (ABR) threshold were found. After transplantation of neural differentiated hMSCs, the number of SGNs was increased, and some of the SGNs expressed immunoreactivity with human nuclear antibody under confocal laser scanning microscopy. ABR results showed mild hearing recovery after transplantation. Based on an auditory neuropathy animal model, these findings suggest that it may be possible to replace degenerated SGNs by grafting stem cells into the scala tympani.

Cobalt, chromium and molybdenum ions kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication.

INTRODUCTION: A patient with a total hip replacement developed optic, acoustic and peripheral neuropathy from metal ions intoxication, due to the wear products released from the prosthesis. Subsequently the kinetics of the metal ions was studied. MATERIALS AND METHODS: Massive wear and acute intoxication allowed a study of the metal ions kinetics and of EDTA treatment. RESULTS: Plasma and other organic fluids were saturated by each of the metal ions released from the exposed surface according to the solubility of each ion; a larger fraction of Co ions was bound within red cells, while the plasmatic fraction appeared more movable. In a patient with a prosthesis subjected to wear, the ions released are from the prosthetic and from the debris surface (spread in the body). The latter is a function of the number and size of particles. DISCUSSION: Revision of the prosthesis from the point of view of the metal ions kinetics corresponded to a reduction of the releasing surface because of debris washed out by irrigation and tissue excision; however, the metal particles spread by lymphatic circulation continued to release ions even though the source of wear had been removed. Early diagnosis of high metal wear can be ascertained with mass spectrometry and after revision high levels of metal ions can only be reduced with repeated chelating treatment. It is preferable not to revise fractured ceramic components with a polyethylene-metal articulation.

Acquired auditory neuropathy spectrum disorder after malaria treated with quinine.

Auditory neuropathy spectrum disorder (ANSD) can cause significant hearing impairment; it occurs when there is intact outer hair cell function in the inner ear, with a dyssynchronous neural response, thought to be due to dysfunction of the inner hair cells (IHCs), the synapse of the IHCs and the auditory nerve, or of the auditory nerve itself. This case report describes the onset of ANSD in a Malawian child after severe malaria treated with quinine. Diagnosis of ANSD was made by confirming the presence of otoacoustic emissions, together with the absence of auditory brainstem response and absent acoustic reflexes.

Assessment of central auditory processing in a group of workers exposed to solvents.

CONCLUSION: Despite having normal hearing thresholds and speech recognition thresholds, results for central auditory tests were abnormal in a group of workers exposed to solvents. Workers exposed to solvents may have difficulties in everyday listening situations that are not related to a decrement in hearing thresholds. A central auditory processing disorder may underlie these difficulties. OBJECTIVE: To study central auditory processing abilities in a group of workers occupationally exposed to a mix of organic solvents. MATERIALS AND METHODS: Ten workers exposed to a mix of organic solvents and 10 matched non-exposed workers were studied. The test battery comprised pure-tone audiometry, tympanometry, acoustic reflex measurement, acoustic reflex decay, dichotic digit, pitch pattern sequence, masking level difference, filtered speech, random gap detection and hearing-in-noise tests. RESULTS: All the workers presented normal hearing thresholds and no signs of middle ear abnormalities. Workers exposed to solvents had lower results in comparison with the control group and previously reported normative data, in the majority of the tests.

Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation.

Neurons at higher stages of sensory processing can partially compensate for a sudden drop in peripheral input through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where >95% of afferent synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, auditory cortex (ACtx) processing and perception recover despite the absence of an auditory brainstem response (ABR) or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC), an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB) of awake mice. Sound driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory plasticity at the level of the auditory thalamus was less robust overall than previous observations in cortex or midbrain. Hierarchical differences in compensatory plasticity following sensorineural hearing loss may reflect differences in GABA circuit organization within the MGB, as compared to the ACtx or IC.

Prenatal low dosage dioxin (TCDD) exposure impairs cochlear function resulting in auditory neuropathy.

2,3,7,8-tetrachorodibenzo-p-dioxin (TCDD), a ubiquitous and persistent environmental contaminant, is a potent teratogen. Whereas developmental TCDD toxicity is mediated by the aryl hydrocarbon receptor (AhR), the normal function of the AhR is poorly understood. We tested whether dioxin exposure during a critical period of hair cell development disrupts cochlear function in three mouse strains, (C57BL6, BalbC, and CBA) that contain high affinity AhR-b alleles. C57BL/6, BalbC, and CBA dams were exposed to 500 ng/kg TCDD or olive oil (vehicle) on embryonic day 12 by gavage. Cochlear function was analyzed at 1.5 months of age by measuring 1) auditory brainstem response (ABRs) to tone pips from 5.6 to 30 kHz, and 2) distortion-product otoacoustic emissions (DPOAEs) evoked by primaries with f2 at the same frequency values. Cochlear threshold sensitivity following TCDD exposure was significantly elevated in both female and male mice in the C57BL/6 strain, carrying the Ahb-1 allele, but not significantly elevated in the BalbC or CBA strains, carrying the Ahb-2 allele. These ABR threshold deficits in mice carrying the Ahb-1 allele parallels the cleft palate incidence to higher TCDD exposures, suggesting that ABR testing could serve as a sensitive indicator of TCDD toxicity in at-risk children. Moreover, DPOAEs were not affected following TCDD exposure in any of the mouse strains, suggesting that following TCDD exposure mice with the Ahb-1 allele exhibit a mild auditory neuropathy. The causes of many auditory neuropathies are unknown, yet a developmental exposure to dioxin may be a risk factor for this condition.

Neurotoxic effects of mercury on auditory cortex networks growing on microelectrode arrays: a preliminary analysis.

Mercury is known to cause sensorineural hearing loss and impaired speech perception. However, there is still a lack of a quantitative description of mercury toxicity on central auditory structures. This is a preliminary study using the novel technique of microelectrode array (MEA) recordings to evaluate acute and chronic neurotoxic effects of mercury on auditory cortex networks (ACNs) in vitro. Morphological and electrophysiological effects of mercuric chloride (HgCl(2)) were studied. Neurons dissociated from auditory cortices of 14-day-old mouse embryos were grown on photoetched MEAs containing 64 transparent indium-tin oxide (ITO) electrodes. For acute electrophysiological experiments, the spontaneous spiking and bursting activity from ACNs were compared before and after application of HgCl(2). For chronic electrophysiological experiments, auditory cortex cultures were treated with various concentrations of HgCl(2) from the day of seeding, and were tested 4 weeks later for the presence of spontaneous activity. Morphological analysis was conducted on 8-day-old ACNs treated with HgCl(2) for 3 days. Results of acute experiments indicated that <75 mM of HgCl(2) had an excitatory effect of variable magnitude on the spontaneous activity of ACNs; however, concentrations above 100 microM completely and irreversibly inhibited spike and burst activity. Chronic exposure of ACNs to 10 microM HgCl(2) completely blocked the spontaneous activity. Morphological analysis indicated that 10 microM HgCl(2) caused neuronal cell death in 3 days. It is concluded that HgCl(2) has a more toxic effect on auditory networks when exposed chronically, and the levels of mercury showing toxic effects on ACNs are within the dose range shown to cause neurologic symptoms in humans.

A characteristic of aspirin-induced hearing loss in auditory brainstem response of conscious rats.

The acute effects of aspirin on auditory functions were examined electrophysiologically in conscious rats with chronically implanted electrodes for auditory brainstem response (ABR) recording. A single intravenous injection of aspirin at a dose of 225 mg/kg caused a reduction in the amplitude of the ABR P1 wave evoked by a 2 kHz tone pip 1 and 24 hr after dosing at almost all sound intensity levels, while the P1 amplitude at 4 kHz was reduced mainly 1 hr after dosing, and the P1 amplitude at 8 kHz was not significantly affected at middle and high intensities even 1 hr after dosing. The audiogram obtained from the P1 amplitude showed a significant increase in the sound threshold 1 and 24 hr after dosing at 2 kHz, and 1 hr after dosing at 4 kHz, but not at 8 kHz. The peak latency of the P1 wave was also prolonged. Furthermore, reduction of the P2 and P4 wave amplitude and prolongation of the P1-P2 and P2-P4 interpeak latency were also observed at 2 kHz but not a 4 or 8 kHz. These results suggest that the rat auditory function for low frequency is vulnerable to the effects of aspirin. This paradigm, i.e., frequency selectivity, n rats may be useful to further assess the different outer hair cells along the cochlear duct and provide additional evidence for the mechanism(s) or site underlying aspirin ototoxicity.

[Peripheral and central auditory effects of pesticide exposure: a systematic review]. / Efeitos da exposição a agrotóxicos sobre o sistema auditivo periférico e central: uma revisão sistemática.

The World Health Organization reports a total of 3 million annual cases of acute pesticide poisoning (2.1 million cases in the developing countries alone). Pesticide use has reached alarming proportions in Brazil in the last decade. Pesticide sales skyrocketed from 2001 to 2008, making Brazil the world's leading consumer of poisons. This study aimed to assess whether pesticide exposure causes peripheral or central auditory disorders and thus focused on the importance of hearing tests in populations with acute or chronic exposure. This was a systematic review of studies on the effects of pesticide exposure on the auditory system. The context and methodological quality of the full texts were analyzed. The review identified 143 studies on the theme, 16 of which met the inclusion criteria. All articles showed that pesticide exposure is ototoxic and leads to hearing loss.

High doses of cobalt induce optic and auditory neuropathy.

The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.

Protective effect of edaravone against tobramycin-induced ototoxicity.

CONCLUSION: It is suggested that simultaneous treatment with the radical scavenger edaravone has an effective protective effect against tobramycin ototoxicity in rat. Even if the edaravone treatment is postponed for 7 days, it can still prevent hearing loss, but a 14 day delay cannot protect from ototoxicity. OBJECTIVES: With the aim of alleviating hearing loss caused by aminoglycoside ototoxicity, we performed a trial to assess the hearing protective efficacy of the radical scavenger edaravone. MATERIALS AND METHODS: In part one of the study, 21 male Sprague-Dawley albino rats were used; 2 rats served as controls for the safety of edaravone. Eight rats each received 10 subcutaneous injections (s.c.) of tobramycin (160 mg/kg b.w.) once daily and saline injection intraperitoneally for 2 weeks. Eleven rats were given 10 s.c. tobramycin injections simultaneously with an intraperitoneal injection of edaravone (3 mg/kg b.w.). In part two, tobramycin was injected in 13 rats (as above). Five of these received two edaravone injections 7 days later and four rats similarly 14 days later. Auditory brainstem response (ABR) was used to assess hearing. RESULTS: All rats treated only with tobramycin showed a deterioration of hearing. None of the rats given simultaneous treatment with tobramycin and edaravone demonstrated hearing loss. A 7 day delay in edaravone injection still prevented hearing loss, but a 14 day delay had only a temporary prophylactic effect.

Efeitos da exposição a agrotóxicos sobre o sistema auditivo periférico e central: uma revisão sistemática / Peripheral and central auditory effects of pesticide exposure: a systematic review / Efectos de la exposición a los pesticidas en el sistema auditivo periférico y central: una revisión sistemática

De acordo com a Organização Mundial da Saúde, as intoxicações agudas por agrotóxicos são da ordem de 3 milhões anuais, com 2,1 milhões de casos só nos países em desenvolvimento. Na última década, no Brasil, o uso de agrotóxicos assumiu proporções assustadoras. Entre 20012008 a venda desses produtos saltou, quando o país alcançou a posição de maior consumidor mundial de venenos. O objetivo deste estudo foi avaliar por meio de uma revisão sistemática se a exposição ao agrotóxico causa alterações auditivas no sistema auditivo periférico/central, atentando assim para a importância da avaliação auditiva em populações expostas de forma crônica ou aguda. Trata-se de uma revisão sistemática dos estudos publicados sobre os efeitos da exposição ao agrotóxico no sistema auditivo. Analisaram-se os trabalhos contemplados na íntegra e também sua qualidade metodológica. A pesquisa identificou 143 estudos sobre o tema, sendo que 16 se enquadraram nos critérios de inclusão. Todos os artigos analisados evidenciaram que a exposição ao agrotóxico é ototóxica e induz ao dano às vias auditivas.

The World Health Organization reports a total of 3 million annual cases of acute pesticide poisoning (2.1 million cases in the developing countries alone). Pesticide use has reached alarming proportions in Brazil in the last decade. Pesticide sales skyrocketed from 2001 to 2008, making Brazil the world's leading consumer of poisons. This study aimed to assess whether pesticide exposure causes peripheral or central auditory disorders and thus focused on the importance of hearing tests in populations with acute or chronic exposure. This was a systematic review of studies on the effects of pesticide exposure on the auditory system. The context and methodological quality of the full texts were analyzed. The review identified 143 studies on the theme, 16 of which met the inclusion criteria. All articles showed that pesticide exposure is ototoxic and leads to hearing loss.

El objetivo de este artículo es presentar un estudio sobre el uso de la historia oral de vida como estrategia de aproximación entre cuidador y anciano, con el fin de contribuir a la humanización en la relación entre el profesional de la salud y el paciente. Se trata de una investigación cualitativa y descriptiva. Hemos reunido a siete ancianos, varones y mujeres, con más de 65 años que, a partir de entrevistas abiertas y semi-estructuradas, hicieron posible la producción de relatos de vida que, una vez finalizados, fueron devueltos a los colaboradores en forma de cuadernos personalizados para que ellos dispusieran de ellos como quisieran. Como resultado ha sido posible percibir que tal metodología contribuye a la generación de un vínculo entre enfermero y anciano, presentándose no solamente como elemento humanizador, sino también terapéutico.

Hearing loss after continuous or single-shot spinal anesthesia.

BACKGROUND AND OBJECTIVES: Hearing loss after spinal anesthesia is probably caused by cerebrospinal fluid (CSF) leakage. Spinal catheters may mechanically plug the hole in the dura and cause inflammatory swelling which should prevent cerebrospinal fluid leakage and hearing loss. An audiometric evaluation was therefore performed in patients who had spinal anesthesia by single-shot or catheter. METHODS: Twenty-one patients received single-shot spinal anesthesia and 19 patients continuous spinal anesthesia for orthopedic surgery of the lower limbs. Spinal catheters were removed 24 hours after the start of anesthesia. Audiometry was performed on the day before the operation and on the first, second, and third postoperative day and repeated on the fifth postoperative day, if necessary. RESULTS: The frequency of hearing impairment (threshold change > 10 dB) was 43% in the single-shot and 37% in the continuous spinal group. The deterioration lasted longer in the continuous spinal group (3 days vs. 1.4 days; P < .01). CONCLUSION: Although inflammatory swelling of the dura mater around the spinal catheter had been observed, use of such a catheter for 24 hours did not prevent hearing loss after its removal.

Sensorineural hearing loss as evidenced by the auditory brainstem response following prenatal cocaine exposure in the Long-Evans rat.

Prenatal cocaine exposure has been associated with a variety of adverse neurological effects. Three recent studies found evidence that prenatal cocaine exposure is associated with abnormal auditory electrophysiology, suggesting abnormal processing of auditory information. The present study used the auditory brainstem response to evaluate the effects of prenatal cocaine exposure on hearing in an animal model (Long-Evans rat). We report that prenatal cocaine exposure can cause elevated ABR thresholds and latency-intensity curves consistent with a recruitment-type sensorineural hearing loss.

[Monitoring hearing during ototoxic cisplatin therapy]. / Zur Uberwachung des Gehörs während der ototoxischen Cisplatin-Therapie.

In the 1983-1988 period, the audition of 17 children was studied prior to and during antineoplastic chemotherapy with cumulative total cisplatin doses from 270 to 1530 mg/m2. The hearing tests were conducted by means of an objective method which doses not depend on patients' cooperation: the recording of fast auditory evoked potentials. Tone threshold audiograms were additionally obtained from cooperative children. Of the 17 patients, 14 showed a dose-dependent symmetric hearing loss which in part was severe and related in particular to the high-frequency domain. Three patients exhibited no hearing impairment even though the total cisplatin dose applied ranged from 630 to 810 mg/m2. To conclude, while allowing for reports in the literature, recommendations are given on how hearing impairment can be minimised in view of the priority of the antineoplastic action of cisplatin.