Jean-Marie Aran

Acute and chronic effects of aminoglycosides on cochlear hair cells.

ABSTRACT: The first detectable effect on the auditory system after a single high‐dose injection of an aminoglycosidic antibiotic (AA) like gentamicin (GM) is the reversible blockade of medial efferent function, probably via blockade of calcium channels at the base of the outer hair cells (OHC). The kinetics of this effect are compatible with that of the molecule in perilymph. In the course of chronic treatment with lower doses, however, ototoxicity develops only after several days of treatment. Still GM can be observed inside the OHCs as soon as 24 hours after the first injection, and will be still present in some OHCs as long as 11 months after a chronic, nonototoxic 6‐day treatment.

Electrophysiological measures of cochlear function in guinea pigs with long-term endolymphatic hydrops

Experimental endolymphatic hydrops was induced in guinea pigs by obliteration of the endolymphatic sac and duct. From 3 to 24 months after this operation, cochlear action potential (AP) audiograms and AP tuning curves were measured. The purpose of this study was to establish parallels, if any, between this supposed animal model of Menières disease and the auditory symptoms of the disease in man. In some animals, low and middle frequency AP threshold elevations were observed whilst higher frequency regions maintained normal sensitivity. Other animals developed flat or very gradually sloping AP audiograms. These patterns are qualitatively similar to those found clinically in Menières disease. AP tuning curves measured in frequency regions of threshold elevation indicated a deterioration of cochlear frequency selectivity; psychophysical and electrocochleographic studies demonstrate related changes in Menières patients. One animal exhibited modifications in AP thresholds and tuning as a result of glycerol administration. These observations improve our confidence in the validity of this animal model for further studies of the pathophysiology of Menières disease.

Frequency sensitivity and selectivity of acoustically evoked potentials after complete cochlear hair cell destruction

Abstract After complete destruction of cochlear but preservation of vestibular hair cells in guinea pigs acoustic stimuli can still evoke neural responses but of unusual features. Measures of thresholds in such cases revealed a rather flat frequency sensitivity curve from 63 Hz to 16 kHz. Clear tuning could also be observed as in normal or pathological cases with cochlear hair cells. These results make these peculiar acoustic responses akin to those originating from hearing organs.

Changes in Auditory Brainstem Responses in Alpha-linolenic Acid Deficiency as a Function of Age in Rats

Auditory brainstem responses (ABRs) to click stimuli have been compared in young (21-day-old), adult (6-month-old), and old (18-month-old) rats fed a normal (Arachid-Colza) or an alpha-linolenic acid deficient (Arachid only) diet. Wave I amplitude and latency did not show any significant change with either age or diet. However, wave III showed a progressive decrease in amplitude and latency from young to adult and from adult to old rats having a normal diet. With alpha-linolenic acid deficiency, wave III amplitude and latency values decreased faster than in the normal diet control groups. Although final values in the old groups with the two diets were similar, with alpha-linolenic acid deficiency values for wave III decreased to this final level in the adult group. These data indicate that the central auditory nervous system ages faster, or earlier, with a fatty acid deficiency.

Electrical Stimulation of the Ear: Experimental Studies:

The possibility of stimulating the ear by way of an electrode on the round window in order to relieve tinnitus or to produce auditory sensations has been investigated experimentally in guinea pigs. The deleterious effects of DC currents applied to a normal cochlea clearly demonstrate that this means is unsuitable for use in relieving tinnitus in hearing patients. Although AC currents do not cause further damage in ears with the organ of Corti already destroyed by aminoglycosides, the effects of DC currents in such cases have still to be investigated before they can be recommended for the relief of tinnitus in totally deaf patients. Electrical stimulation of the round window combined with masking has made it possible to record responses of auditory neural elements from the eighth nerve to the auditory cortex. This technique could be promising for the basic study of the central auditory nervous system, both experimentally and clinically, and could lead to a more accurate evaluation of candidates for cochlear prostheses.

Effects of exposure of the ear to GSM microwaves: in vivo and in vitro experimental studies

The effects of mobile phone (GSM) microwaves on the ears of guinea pigs were investigated in two in vivo experiments and one in vitro experiment. In the first experiment, three groups of eight guinea pigs had their left ear exposed for 1 h/day, 5 days/week, for 2 months, to GSM microwaves (900 MHz, GSM modulated) at specific absorption rates (SARs) of 1, 2 and 4 W/kg respectively, and a fourth group was sham-exposed. Distortion-product otoacoustic emissions (DPOAEs) were measured for each ear before exposure, at the end of the 2-month exposure period, and 2 months later. In the second experiment, the same protocol was applied to eight sham-exposed and 16 exposed guinea pigs at 4 W/kg, but the auditory brainstem response (ABR) thresholds were monitored. Repeated-measures ANOVA showed no difference in DPOAE amplitudes or in ABR thresholds between the exposed and non-exposed ears and between the sham-exposed and exposed groups. In the course of the second experiment, acute effects were also investigated by measuring once, in all animals, ABR thresholds just before and just after the 1-h exposure: no statistically significant difference was observed. In vitro, the two organs of Corti (OCs) of newborn rats (n = 15) were isolated and placed in culture. For each animal, one OC was exposed for 24–48 h to 1 W/kg GSM microwaves, and the other was sham-exposed. After 2–3 days of culture, all OCs were observed under light microscopy. They all appeared normal to naive observers at this stage of development. These results provided no evidence that microwave radiation, at the levels produced by mobile phones, caused damage to the inner ear or the auditory pathways in our experimental animals. Sumario Se investigaron los efectos de las micro-ondas (GSM) de los teléfonos móviles sobre los oídos de los cobayos en dos experimentos in vivo y en uno in vitro. En el primer experimento, 3 grupos de 8 cobayos (GP) tuvieron su oído izquierdo expuesto durante 1 hora/día, 5 días/semana, por 2 meses, a micro-ondas GSM (900 MHz, con modulación GSM) con Tasas de Absorción Específica (SAR) de 1, 2 y 4 W/kg, respectivamente, y un cuarto grupo tuvo una exposición fingida. Se midieron emisiones otoacústicas por productos de distorsión (DPOAE) antes, al final del período de exposición de 2 meses y 2 meses después. En el segundo experimento, se aplicó el mismo protocolo con 8 exposiciones fingidas y 16 GP expuestos a 4 W/kg, pero se monitorizaron los umbrales de las Respuestas Auditivas del Tallo Cerebral (ABR). Las mediciones repetidas ANOVA no mostraron diferencia en las amplitudes de los DPOAE o en los umbrales de las ABR entre oído expuestos y no expuestos, y entre los grupos con exposición verdadera y fingida. En el curso del segundo experimento, se consideraron los efectos agudos midiendo una vez, en todos los animales, los umbrales ABR inmediatamente antes y una hora después de la exposición: no se observó una diferencia estadísticamente significativa. In vitro, se aislaron y colocaron en cultivo dos órganos de Corti (OC) de ratas recién nacidas. Para cada animal, un OC fue expuesto por 24-48 horas a micro-ondas GSM de 1-W/kg; el otro se sometió a una exposición fingida. Luego de días adicionales en cultivo, todos los OC fueron observados bajo microscopía de luz. Ante observadores independientes, todos lucieron normales en esa etapa de crecimiento. Los resultados no muestran evidencia de que la radiación por micro-ondas, a los niveles producidos por los teléfonos móviles, puedan causar daño en el oído interno o en las vías auditivas de nuestros modelos experimentales.

Bioelectrical cochlear noise and its contralateral suppression : relation to background activity of the eighth nerve and effects of sedation and anesthesia

Abstractu2002The bioelectrical activity of the cochlea, without any ipsilateral acoustic stimulation, was recorded in awake guinea pigs (GPs) between electrodes chronically implanted at the round window (RW) and the skull. Measuring its power in the band centered around 1.0 kHz (0.5–2.5 kHz) provided an indirect measure of the ensemble background (EBA) activity of the eighth nerve. Contralateral white-noise (CLWN) stimulation reduced this EBA, presumably by activation of medial olivocochlear fibers. The aim of the investigation was to validate measurements of EBA and of its contralateral suppression in order to study the medial efferent function. The first goal was to find the best conditions for recording the EBA in the absence of ipsilateral stimulation and for studying its suppression by contralateral acoustic stimulation, which implies that no noise was generated by the experimental animal. Thus recordings were compared in normal, awake GPs and in GPs under sedation with xylazine, anesthetized with a combination of xylazine and ketamine, and with and without temperature regulation. In order to monitor the effects of sedation and anesthesia, the recordings were analyzed not only in the 0.5- to 2.5-kHz frequency band but also in the other frequency bands, 5–50 Hz, 50–150 Hz, and 150–500 Hz, which presumably include general central and neuromuscular contributions. The results show that sedation with xylazine accompanied by regulation of body temperature does not affect the EBA value nor its contralateral suppression. Nevertheless, anesthesia should be avoided, even with control of body temperature. The second goal of this study was to identify the specific cochlear contribution to the raw RW signal. Thus recordings were performed in normal and deafened animals and analyzed in the frequency band 0.5–2.5 kHz and also in the other frequency bands of 5–50 Hz, 50–150 Hz, and 150–500 Hz. The results indicate that most of the cochlear activity lies in the frequency band 0.5–2.5 kHz, with also some minor contribution coming from the 150- to 500-Hz band. Analysis and comparison of power values in the different conditions indicate that specific cochlear EBA power was about 60 μV2. From a commonly accepted mean background discharge rate of 50 spikes/s (sp/s), the EBA power without CLWN should have been around 4.4 μV2 if the fibers’ activity was random. This difference suggests that there is probably some degree of synchrony between individual fibers. There was a reduction of approximately 45% during CLWN stimulation. This suppression might correspond to a reduction in both discharge rate and synchrony of the fibers.

Intracochlear electrical tinnitus reduction.

Several reports have indicated that some cochlear implant patients experience a reduction in their tinnitus while listening to noise or speech. In the present study, two patients reporting bilateral tinnitus were selected from a group of adults with the Nucleus cochlear implant. They rated their tinnitus loudness and severity and completed the Tinnitus Handicap Questionnaire. The stimuli for electrical stimulation were charge-balanced pulse trains of various repetition rates (frequencies) and inter-electrode distances. A range of electrodes was chosen in each subject, including basal, medial and apical electrodes. For each condition, the hearing threshold level and the uncomfortable loudness level were determined. A range of stimulus levels between these two values were presented randomly. After each presentation, the patients rated the stimulus loudness and the tinnitus loudness on a 0 to 100 scale. These judgements were used to carefully determine the psychometric function between stimulus level and stimulus loudness, and between stimulus level and tinnitus loudness. All the parameters explored were important for maximizing the relationship between tinnitus reduction and stimulus loudness. First, the effectiveness of electrical stimulation in tinnitus reduction depended on the place along the cochlear partition. Second, a pulse rate of 125 Hz showed the greatest efficiency in terms of the current level needed to suppress tinnitus. Third, these two subjects showed rather poor performances in speech perception when using their speech processor in the usual condition and the hypothesis of an influence from tinnitus annoyance is suggested in addition to some more classical predicting factors of speech recognition in cochlear implant users.

Chronic exposure to an environmental noise permanently disturbs sleep in rats: Inter-individual vulnerability

Chronic exposure to an environmental noise (EN) induces sleep disturbances. However, discrepancies exist in the literature since many contradictory conclusions have been reported. These disagreements are largely due to inappropriate evaluation of sleep and also to uncontrolled and confounding factors such as sex, age and also inter-individual vulnerability. Based on a recently validated animal model, aims of the present study were (i) to determine the effects of a chronic exposure to EN on sleep and (ii) to evaluate the inter-individual vulnerability of sleep to EN. For this purpose, rats were exposed during 9 days to EN. Results show that a chronic exposure to EN restricts continually amounts of slow wave sleep (SWS) and paradoxical sleep (PS) and fragments these two sleep stages with no habituation effect. Results also evidence the existence of subpopulations of rats that are either resistant or vulnerable to these deleterious effects of EN on sleep and especially on SWS amounts, bouts number and bout duration. Furthermore, importance of SWS debt and daily decrease of SWS bout duration are correlated to each others and both correlate to the amplitude of the locomotor reactivity to novelty, a behavioral measure of reactivity to stress. This last result suggests that this psychobiological profile of subjects, known to induce profound differences in neural and endocrine systems, could be responsible for their SWS vulnerability under a chronic EN exposure.

Deleterious effects of an environmental noise on sleep and contribution of its physical components in a rat model

Sleep disturbances induced by environmental noise (EN) exposure are now well admitted. However, many contradictory conclusions and discrepancies have been reported, resulting from uncontrolled human factors or the use of artificial noises (pure tone). Thus, the development of an animal model appears to be a useful strategy for determining whether EN is deleterious to sleep. The aims of this study were: (i) to confirm the effects of noise on sleep in a rat model; and (ii) to determine the most deleterious physical component of noise regarding sleep structure. For this purpose, rats were exposed during 24 h either to EN or to artificial broad-band noises [either continuous broad-band noise (CBBN) or intermittent broad-band noise (IBBN)]. All the noises decrease both slow wave sleep (SWS) and paradoxical sleep (PS) amounts during the first hours of exposure. However, CBBN acts indirectly on PS through a reduction of SWS bout duration, whereas IBBN and EN disturb directly and more strongly both SWS and PS. Finally, EN fragments SWS and decreases PS amount during the dark period, whereas IBBN only fragments PS. These results demonstrate the validity and suitability of a rodent model for studying the effects of noise on sleep and definitively show that sleep is disturbed by EN exposure. Two physical factors seem to be implicated: the intermittency and the frequency spectrum of the noise events, which both induce long-lasting sleep disturbances. An additive effect of frequency spectrum to intermittency tends to abolish all possible adaptations to EN exposure. Since sleep is involved in cognitive processes, such disturbances could lead to cognitive deficits.