Search

SIGNIFICANCE Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose-limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including: redox imbalance caused by reactive oxygen species (ROS) production and lipid peroxidation, activation of inflammation, p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies in order to reduce side effect toxicities while preserving or enhancing the anti-neoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, i.e. normal cells undergoing stressful conditions versus cancer cells. CRITICAL ISSUES This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/crosstalk between the cell's defenses, inflammatory molecules, and the key signaling molecules of STAT-3, NF-κB, p53, and Nrf-2. FUTURE DIRECTIONS We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols.

The cross-talk between oxidative stress and inflammation seems to play a key role in noise-induced hearing loss. Several studies have addressed the role of PPAR receptors in mediating antioxidant and anti-inflammatory effects and, although its protective activity has been demonstrated in several tissues, less is known about how PPARs could be involved in cochlear dysfunction induced by noise exposure. In this study, we used an in vivo model of noise-induced hearing loss to investigate how oxidative stress and inflammation participate in cochlear dysfunction through PPAR signaling pathways. Specifically, we found a progressive decrease in PPAR expression in the cochlea after acoustic trauma, paralleled by an increase in oxidative stress and inflammation. By comparing an antioxidant (Q-ter) and an anti-inflammatory (Anakinra) treatment, we demonstrated that oxidative stress is the primary element of damage in noise-induced cochlear injury and that increased inflammation can be considered a consequence of PPAR down-regulation induced by ROS production. Indeed, by decreasing oxidative stress, PPARs returned to control values, reactivating the negative control on inflammation in a feedback loop.

Background Although styrene is an established ototoxic agent at occupational exposure levels, the mechanisms of styrene toxicity in the auditory system are still unclear. Objectives The aim of this study was to identify the consequences of styrene chronic exposure in cochlear structures, looking for the mechanisms of ototoxicity of this organic compound and focusing on cell targets and oxidative stress/inflammatory processes. Methods Male adult Wistar rats were exposed to styrene (400 mg/kg by gavage for 5 days/week, 3 consecutive weeks). Hearing loss was evaluated by measuring auditory brainstem responses (ABR), morphological analysis were performed to evaluate hair cell and spiral ganglion neuron survival, as well as synaptic damage. Analysis of apoptotic (p53) and inflammatory (NF-κB, TNF-α, IL-1β and IL-10) mediators were performed by immunofluorescence analysis and western blot. Results Styrene ototoxic effects induced a hearing loss of about 35–40 dB. Immunofluorescence and western blotting analyses demonstrated that styrene administration induced redox imbalance and activated inflammatory processes, targeting sensory hair cell and neural dysfunction by a cross-talk between oxidative and inflammatory mediators. Discussion Major findings connect styrene ototoxicity to an interplay between redox imbalance and inflammation, leading to the intriguing assumption of a mixed sensory and neural styrene-induced ototoxicity. Thus, in a clinical perspective, data reported here have important implications for styrene risk assessment in humans.

HYPOTHESIS: Trans-tympanic Rosmarinic Acid (RA), as compared with the systemic administration, protects against noise-induced auditory hair cell and hearing losses in rats in vivo. BACKGROUND: ROS production, lipoperoxidative damage, and an imbalance of antioxidant defences play a significant role in noise-induced hearing loss. Several molecules with antioxidant properties have been tested to restore redox homeostasis; however, drug delivery system represents a challenge for their effectiveness. In our model, acute and intense noise exposure induces hearing loss, hair cell death, and oxidative stress, with an increase in superoxide production and over-expression of lipid peroxidation in cochlear structures. METHODS: RA was administrated in male Wistar rats by trans-tympanic (20 μl) and systemic (10 mg/kg) modality. In systemic administration, RA was injected 1 hour before noise exposure and once daily for the following 3 days. ABRs were measured before and at days 1, 3, 7, and 30 after noise exposure. Rhodamine-phalloidin staining, dihydroethidium and 8-isoprostane immunostainings were performed to assess and quantify outer hair cells loss, superoxide production, and lipid peroxidation in the different experimental groups. RESULTS: Systemic RA administration significantly decreased noise-induced hearing loss and the improvement of auditory function was paralleled by a significant reduction in cochlear oxidative stress. The trans-tympanic modality of drug administration showed a similar degree of protection both at the functional and morphological levels. CONCLUSION: The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

This study addresses the relationship between cochlear oxidative damage and auditory cortical injury in a rat model of repeated noise exposure. To test the effect of increased antioxidant defenses, a water-soluble coenzyme Q10analog (Qter) was used. We analyzed auditory function, cochlear oxidative stress, morphological alterations in auditory cortices and cochlear structures, and levels of coenzymes Q9and Q10(CoQ9and CoQ10, respectively) as indicators of endogenous antioxidant capability. We report three main results. First, hearing loss and damage in hair cells and spiral ganglion was determined by noise-induced oxidative stress. Second, the acoustic trauma altered dendritic morphology and decreased spine number of II–III and V–VI layer pyramidal neurons of auditory cortices. Third, the systemic administration of the water-soluble CoQ10analog reduced oxidative-induced cochlear damage, hearing loss, and cortical dendritic injury. Furthermore, cochlear levels of CoQ9and CoQ10content increased. These findings indicate that antioxidant treatment restores auditory cortical neuronal morphology and hearing function by reducing the noise-induced redox imbalance in the cochlea and the deafferentation effects upstream the acoustic pathway.

Sinusoidal vestibular stimulation induces in the intact rabbit in prone position a periodic alternating drift (PAD), evident in the earth horizontal plane when the animal is rotated about the vertical axis but weak in the vertical one when the animal is rotated about the longitudinal axis. It has been hypothesized that these oscillations are related to an intrinsic instability of the velocity storage, due to the length of its time constant. The velocity storage has the longest time constant aligned with the vertical axis, and it changes its orientation with the gravity vector. The present research examined the spatial orientation of PAD in relation to changes of the animal position with respect to gravity. Normal pigmented rabbits were sinusoidally oscillated about their longitudinal axes to evoke vertical eye responses. The stimulation was carried out with the animal in prone position and with the animal in nose-up condition. With the animal in prone position, PAD had a weak vertical component, but an evident horizontal component was visible. When the animal was in nose-up position, the horizontal component of PAD was clearly visible, while the vertical component was negligible. In both stimulation conditions PAD period and peak velocity were not modulated by the stimulus characteristics. These results are consistent with a model of PAD based on an interaction between velocity storage and the cerebellar adaptation-habituation circuit.

Background: In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo. Methods: The effects of curcumin and/or cisplatin treatment have been evaluated in head and neck squamous cell carcinoma as well as in a rat model of cisplatin-induced ototoxicity by using immunofluorescence, western blot, and functional and morphological analysis. Results: This study demonstrates that curcumin attenuates all stages of tumour progression (survival, proliferation) and, by targeting pSTAT3 and Nrf-2 signalling pathways, provides chemosensitisation to cisplatin in vitro and protection from its ototoxic adverse effects in vivo. Conclusions: These results indicate that curcumin can be used as an efficient adjuvant to cisplatin cancer therapy. This treatment strategy in head and neck cancer could mediate cisplatin chemoresistance by modulating therapeutic targets (STAT3 and Nrf2) and, at the same time, reduce cisplatin-related ototoxic adverse effects.

Hypothesis To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. Background Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. Methods In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. Results Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. Conclusion This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

The effectiveness of a coenzyme Q10 formulation, Q-ter, given via transtympanic injection is interesting for the future application of this minimally invasive procedure in the treatment of reactive oxygen species (ROS)-induced hearing loss.We focused on antioxidant therapy in noise-induced hearing loss (NIHL). Our study was designed to evaluate the effectiveness of Q-ter for different schedules of drug administration to establish the best modality for treatment.Rats were exposed to acoustic trauma (10 kHz at 120 dB for 60 min) and received Q-ter according to two modalities: systemic (Q-ter 100 mg/kg for 4 days 1 h before and 3 days post noise exposure) and transtympanic (Q-ter 20 and 40% concentration 1 h before noise exposure). Auditory brainstem response (ABR), immunohistochemical and morphological studies were performed.Q-ter administration significantly decreased NIHL at day 21 from noise exposure. The improvement of auditory function by Q-ter was paralleled by a significant reduction in oxidative stress. The transtympanic and systemic routes of drug administration showed a similar degree of protection.

Conclusion: Our results are in agreement with the general idea that natural antioxidants achieve their best cytoprotective capacity if given before and soon after the stressor. Objective: We focused on ferulic acid (FA, 4-hydroxy 3-methoxycinnamic acid), a phenolic compound that is known to exhibit antioxidant properties. Our study was designed to evaluate the effectiveness of FA for different schedules of treatment to establish the 'therapeutic window' for FA protection. Methods: Guinea pigs were exposed to acoustic trauma (6 kHz at 120 dB for 60 min) and received a total dose of 600 mg/kg of FA. Group I, noise control; group II, noise + FA (150 mg/kg) for 4 days starting 24 h post exposure; group III, noise + FA (60 mg/kg) 1 h before and 9 days post exposure; group IV, noise + FA (60 mg/kg) given 3 days before and 7 days post exposure; group V, noise + FA (150 mg/kg) 1 h before and 3 days post noise exposure. Auditory brainstem response (ABR) test and immunohistochemical and morphological studies were performed. Results: Group V had significantly decreased noise-induced hearing loss at day 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress marker. The other schedules of drug administration showed a minor degree of protection

Presbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal models.

This study analysed the acoustic and vestibular functional and morphological modifications in guinea pigs after acoustic trauma. Animals were exposed to noise (6 kHz, at 120 dB SPL for 60 minutes) and then auditory brainstem responses (ABR) and vestibuloocular reflex (VOR) were measured at 6 hours, 1 day, 3, 7, and 21 days after noise. Western blotting and immunostaining for 4-hydroxy-2-noneal (4-HNE) and vascular endothelial growth factor (VEGF) were performed in the cochlear and vestibular regions at 1 and 7 days after noise exposure. A significant decrease of VOR gain was observed on day 1 and the recovery was completed at day 21. ABR threshold values reached a level of 80 dB at day 1 after trauma reaching a value of about 50 dB SPL on day 21. 4-HNE expression, a marker of lipid peroxidation was strongly increased in the cochlea. In the vestibule, 4-HNE immunoreactivity was faint. However, VEGF was up-regulated both in the cochlea and vestibule. In conclusion, the expression of VEGF in both cochlear and vestibular structures suggests a reparative role with potentially therapeutic implications.

Idebenone, a synthetic analogue of coenzyme Q, attenuates noise-induced hearing loss by virtue of its antioxidant properties. This study involves a guinea pig model of acoustic trauma where the effectiveness of idebenone is analyzed in comparison with Vitamin E (alpha-tocopherol) that exhibits a potent antioxidant activity in the inner ear. Idebenone and vitamin E were injected intraperitoneally 1 h before noise exposure and once daily for three days; functional and morphological studies were then carried out, respectively, by auditory brainstem responses evaluation, scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay identification of missing and apoptotic cells was also performed. The results showed that the protective effects of idebenone and vitamin E were not additive implying that the two antioxidants may share competitive mechanisms.

Oxidative stress plays a significant role in noise-induced hearing loss (NIHL), as it largely participates in the mechanisms that underlie cell death after noise exposure and lead to sensorineural hearing loss. Many antioxidant drugs have been tested to prevent NIHL. We present three molecules with antioxidant properties (vitamin E, idebenone, N-L-acetylcysteine) that have been studied in our laboratory, and compare their protective effects. We induced acoustic trauma in treated guinea pigs, evaluated their hearing function via electrophysiological measurements at 1, 7 and 21 days, and performed morphological studies with scanning electron microscopy and TUNEL assay. All molecules had a certain effect in protecting hair cells from oxidative stress; vitamin E offered almost complete protection (80–95%), N-L-acetylcysteine and idebenone also significantly reduced the threshold shift and hair cell loss. Our results support the effectiveness of antioxidant drugs in protecting against NIHL and provide a ration...

Idebenone is a synthetic analogue of coenzyme Q10 with antioxidant properties. The present study investigated the antioxidant activity of idebenone in the rescue of acoustic trauma. Noiseinduced hearing loss was induced by exposing guinea pigs to a continuous pure tone and idebenone was injected intraperitoneally 1h before noise exposure and once daily for 3 days. Guinea pigs treated with idebenone showed signi¢cantly smaller auditory threshold shifts than unprotected control animals. Missing and apoptotic cells were identi¢ed with scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. Protected animals presented a lesser extent of both apoptotic activation and hair cell loss in the organ of Corti. Our results suggest an antioxidant function of idebenone in protection from noise-induced hearing loss and provide a rationale for exploring therapeutic strategies in humans. NeuroReport 17:857^ 861 � c 2006 Lippincott Williams & Wilkins.

Saccular and utricular maculae can provide information on the supine static position, considering that both have pronounced curved structures with hair cells having a variety of polarization vectors that enable them to sense an inverted position and thus direct the righting reflex.The vestibular system is essential for the structuring of motor behaviour, senses linear and angular acceleration and has a strong influence on posture and balance at rest, during locomotion and in head body righting reflexes.Using guinea pigs in the supine position with a symmetrical head and trunk position, the ocular position was analysed to ascertain whether any ocular movement that occurred would adopt a spatial deviation indicative of the subsequent head and body righting. The characteristics of the righting reflex (direction, latency, duration and velocity) were analysed in guinea pigs from position signals obtained from search coils implanted in the eye, head and pelvis. The animals were kept in a supine position for a few seconds or even minutes with the eyes in a stable primary position and the head and body symmetrical and immobile.The righting reflex took place either immediately or after a slow deviation of the eyes. In both cases the righting sequence (eyes, head, body) was stereotyped and consistent. The direction of head and body righting was along the longitudinal axis of the animal and was either clockwise or anticlockwise and the direction of righting was related to the direction of the eye deviation. The ocular deviation and the direction of deviation that initiated and determined the direction of the righting reflex could be explained by possible otolithic activation.

The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit.The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans.Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied.During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.

Free radicals are involved in gentamicin ototoxicity and vestibular dysfunction and it has been demonstrated that free radical scavengers, such as alpha-tocopherol, are able to inactive free radicals, attenuating tissue damage This study was designed to investigate the possible protective effects of alpha-tocopherol against gentamicin-induced oto-vestibulo toxicity.Adult albino guinea pigs were divided into four groups and were treated for 2 weeks as follows: Group A, controls; Group B, gentamicin plus corn oil; Group C, gentamicin only; and Group D, gentamicin plus alpha-tocopherol. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VORs), respectively. Electrocochleographic recordings were performed using an implanted round window electrode. The compound action potentials (CAPs) at 2, 4, 8 and 16 kHz were measured every 5 days Morphological changes were analysed by means of scanning electron microscopy.Gentamicin induced a consistent reduction in VOR responses and a progressive high-frequency hearing loss of 50-60 dB sound pressure level. Alpha-Tocopherol co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts The impairment of vestibular function was reduced, as evidenced by an increased VOR gain. The massive loss of outer hair cells in the cochlear basal turn and of cristae ampullaris stereocilia in gentamicin-treated animals was not observed in the cochlea of animals protected with alpha-tocopherol.This study supports the hypothesis that alpha-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in preventing aminoglycoside oto-vestibulo toxicity.

The aim of the present research was to study the participation of trigeminal afferents in head righting reflexes from lateral decubitus. The degree of head righting was measured in 11 guinea pigs before and after unilateral trigeminal section and in 8 bilaterally labyrinthectomized animals before and after unilateral trigeminal neurotomy. All animals were restrained by a body-holder tube to exclude body-righting reflexes acting on the head. Some animals were also blindfolded to avoid the occurrence of optical righting reflexes. In normal animals, the degree of head righting reached a mean value of 70.7°, while after left trigeminal neurotomy, head righting from the operated side underwent a decrement of 18.5°, reaching a mean value of 52.5°. In the 8 bilaterally labyrinthectomized animals, head righting tests revealed a residual righting of 13.5°: the unilateral section of trigeminal nerve completely abolished this partial righting from the side of the sectioned nerve. On the basis of the reported results, in the guinea pig head righting, although mainly triggered by labyrinthine inputs, is also under the influence of trigeminal afferents asymmetrically stimulated by contact with the ground when the animal is placed in lateral decubitus. Thus a “trigeminal head righting reflex” has been demonstrated to contribute to the righting functions.

139 vestibular neurons were analyzed in 38 guinea-pigs after the stimulation of trigeminal fibers: increase or decrease of discharge rate and also rhythmic modulation of vestibular unitary activity were observed.

The activity of 131 vestibular neurons was investigated in 40 guinea pigs during trigeminal stimulation. The influence of trigeminal sensory information was tested by means of electrical stimulation of the trunk of the trigeminal nerve and with nonnociceptive cutaneous stimulation of facial areas. The spontaneous activity of vestibular neurons was modified by trigeminal electrical stimulation with an increase or decrease of the discharge rate. Some units underwent rhythmic modulation. Forty-one percent of recorded units responded also to cutaneous trigeminal stimulation. An analysis of vestibular action potentials evoked by trigeminal stimulation revealed latency values from 1.2 to 6.2 ms. The anatomic-functional relationship between the trigeminal and the vestibular systems is discussed in light of the reported results.

The unilateral section of the trigeminal trunk was performed in 25 guinea pigs after compensation from right hemilabyrinthectomy. To avoid lesion of the cerebral cortex the trigeminal nerve was approached ventrally through the foramina lacerum and ovale which are fused in the guinea pig. Complete section of a trigeminal nerve induced reappearance of already compensated hemilabyrinthectomy symptoms: head and trunk torsion to the right, extension of left forelimb, eye nystagmus to the left, circling and rolling movements to the right, and impairment of body and head righting reflexes from lateral decubitus. These symptoms persisted for 6–8 hr after trigeminal neurotomy. Thus sensory trigeminal afferents seem to contribute to the mechanism of vestibular compensation.

The aim of the research was to analyse the vestibular nuclear activity before and after the section of the 5th cranial nerve in chronically hemilabyrinthectomized guinea pigs during the stage of compensation. The animals were hemilabyrinthectomized (chloroform and vaselin oil into the right middle ear) and upon compensation (24–45 days), field potentials were recorded from the vestibular nuclei of the intact side following electrical stimulation of the ipsilateral labyrinthine receptors. Then the left trigeminal trunk was sectioned ventrally through the foramen lacerum and ovale which are fused in the guinea pig and the vestibular field potentials were again recorded for a period of 120 min. Trigeminal neurotomy modified the vestibular field potentials determining an increment in amplitude of 30–50% of N 1 and N 2 waves, configuration and latency remained unaltered. The dependence of vestibular compensation on trigeminal afferents is discussed on the light of reported results.

In 20 guinea pigs, eye nystagmus of visual origin was investigated following stimulation of an optic nerve (optic nystagmus). The interactions between vestibular and visual inputs were observed by eliciting optic and labyrinthine nystagmus simultaneously. After complete removal of the vestibular nuclei, optic nystagmus was tested: It was no longer elicitable. On that basis, it is possible to conclude that the vestibular nuclei represent an essential station in the mechanism of optic nystagmus.

The behavior of 102 vestibular neurons during optic nystagmus was investigated in 25 guinea pigs with extracellular microelectrodes. The recorded vestibular neurons were electrophysiologically identified by their orthodromic response to ipsilateral labyrinthine stimulation and by antidromic activation from the medial longitudinal fascicle. Of the 102 recorded units, 92 were modulated by the electrical stimulation of at least one optic nerve. The presence of vestibular neurons sensitive to the direction of nystagmus induced by labyrinthine or optic stimulation was also analyzed.

Horizontal eye nystagmus beating towards the stimulated side (‘optic’ nystagmus) was evoked in 25 guinea pigs by stimulating an optic nerve. The complete ablation of the vestibular nuclear complex abolished this nystagmus. In a second group of 15 animals, the behaviour of 63 vestibular neurons identified electrophysiologically was analyzed during eye nystagmus; most of these neurons responded with a tonic increase in discharge rate to stimulation of the optic nerves. Units sensitive to the direction of optic and labyrinthine nystagmus were also identified.

Summary Background To identify a parameter to distinguish normal hearing from hearing impairment in the early stages. The parameter was obtained from transient-evoked otoacoustic emissions (TEOAEs), overcoming the limitations of the usually adopted waveform descriptive parameters which may fail in standard clinical screenings. Material/Methods Audiometric examinations and TEOAE analysis were conducted on 15 normal ears and on 14 hearing-impaired ears that exhibited an audiometric notch around 4 kHz. TEOAE signals were analyzed through a multivariate technique to filter out the individual variability and to highlight the dynamic structure of the signals. The new parameter (named radius 2-dimension – RAD2D) was defined and evaluated for simulated TEOAE signals modeling a different amount of hearing impairment. Results Audiometric examinations indicated 14 ears as impaired-hearing (IH), while the TEOAE ILO92 whole reproducibility parameter (WWR) indicated as IH 7 signals out of 14 (50%). The proposed new parameter indicated as IH 9 signals out of 14 (64%), reducing the number of false negative cases of WWR. Conclusions In this preliminary study there is evidence that the new parameter RAD2D defines the topology and the quantification of the damage in the inner ear. The proposed protocol can be useful in hearing screenings to identify hearing impairments much earlier than conventional pure tone audiometry and TEOAE pass/fail test.