Jean-Paul Erre

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.

Rate influences on tone burst summating potential amplitude in electrocochleography: clinicala and experimentalb data

Electrocochleographic recordings of action and summating potentials are widely used in the electrophysiological assessment of endolymphatic hydrops (ELH). Increased amplitudes of the summating potential (SP) in response to tone burst stimuli are indicative of positive ELH. This study reports the effect of repetition rate of tone burst stimulation on the SP amplitude. Using transtympanic electrocochleography (ECochG), the SP in response to 1 kHz tone bursts was recorded in both a Ménière and a non-Ménière population. Absolute values of the SP were systematically higher in the Ménière group. Moreover, in the Ménière and non-Ménière groups, the response amplitudes of the SP at a repetition rate of 8.4 tone bursts/s were only 66 and 32%, respectively, of the maximal response amplitude which was obtained at the rate of 37.4 tone bursts/s. Additionally, in normal guinea pigs chronically implanted with a round window electrode, the SP was recorded to 0.5-16 kHz tone burst stimulations presented at 100 dB SPL with the same different repetition rates. Similar enhancement of the SP amplitude was observed from 8.4 to 37.4 stimuli/s, whatever the frequency. This effect is interpreted as an increased asymmetry of vibration of the cochlear partition, whose mechanical operating point would not return to the normal resting position at high repetition rates, since it is permanently shifted in ELH.

Electrophysiological Monitoring of the Cochlea During and After Total Destruction of the Organ of Corti

A series of acoustically evoked potentials can be recorded from the cochlea up to the auditory cortex in guinea pigs where the organ of Corti has been totally destroyed after extensive treatment with amikacin, but where some of the spiral ganglion neurons always remain and where the vestibular receptors are only slightly affected. The cochlear responses have been monitored in guinea pigs permanently implanted with a round window electrode and receiving such treatment. The normal auditory nerve compound action potential disappears within a few days, while the very typical response (diphasic, short latency (0.3 ms) small amplitude) appears. This response then remains remarkably constant in time as far as we could observe (up to almost one year). This response might be a component of the normal response, undiscernible under normal conditions but revealed by the selective impairment of the labyrinth by amikacin, in contrast to the global effect of every other known otodestructive agent. Some basic questions still remain: which fibres are effectively stimulated (cochlear or vestibular), what are their central projections, and what kind of sensation is conceivably associated with these responses?

Effects of contralateral acoustical stimulation on three measures of cochlear function in the guinea pig.

The magnitudes of suppression of the click-evoked compound action potential of the auditory nerve (CAP), transient click-evoked otoacoustic emissions (TEOAEs) and ensemble background activity of the auditory nerve (EBA), elicited by contralateral acoustical stimulation, were compared in awake or lightly sedated guinea pigs. The contralateral ear was stimulated either by continuous broad-band noise or by low-pass or high-pass noise (intensity 41-62 dB SPL) with cut-off frequencies of 2, 8 and 12 kHz. The maximal suppression of TEOAEs was achieved by contralateral noise containing mainly low frequencies, whereas for suppression of the CAP it was necessary for middle frequencies to be present in the contralateral noise (less than 8 kHz). In contrast to this, EBA was suppressed mainly by high-frequency noise (higher than 8 kHz) whereas low- and middle-frequency noise was ineffective in suppressing EBA. Evaluation of the root mean square voltage of the EBA (filtered in frequency range 0.75-1.25 kHz) enabled the evaluation of fast and slow components of olivocochlear activation. Both fast and slow effects were proportionally suppressed by individual types of contralateral stimulation. The mechanisms of TEOAEs and CAP generation has been confirmed in many earlier studies, but the origin of EBA has yet to be fully elucidated. The obtained data support the hypothesis that a large part of EBA is formed by spontaneous activity of high-frequency-tuned auditory nerve fibres. Suppression of the EBA magnitude during contralateral stimulation may be caused either by a reduced spontaneous firing rate or by a decrease in possible synchronised neuronal firing.

Changes in electrovestibular brainstem responses after aminoglycoside intoxication in guinea pigs

OBJECTIVEnTo verify the usefulness of short-latency vestibular responses evoked by a combination of round window electrical stimulation and sinusoidal rotation (electrovestibular brainstem responses; EVBRs) as a new monitoring tool of the vestibular function in animal experiments.nnnMETHODSnEVBRs were obtained before, during, and after treatment with aminoglycosides, along with compound action potential (CAP) audiograms. The changes in EVBRs were compared with morphological changes observed by scanning electron microscopy.nnnRESULTSnEVBR amplitudes did not change in the group of guinea pigs treated with amikacin, but markedly decreased in the streptomycin and gentamicin- treated groups. CAP audiograms indicated a significant threshold elevation in the amikacin group, a moderate elevation in the gentamicin group, and no change in the streptomycin group. Under scanning electron microscopy, the loss of the sensory hair cells observed in the cristae ampullares was slight to moderate in the amikacin group, moderate to severe in the streptomycin group, and severe in the gentamicin group.nnnCONCLUSIONnEVBRs reflect overall pathological changes undergone by vestibular hair cells, and support the vestibular specificity of EVBRs.

Role of the Efferent Medial Olivocochlear System in Contralateral Masking and Binaural Interactions: An Electrophysiological Study in Guinea Pigs : Papel del Sistema Olivo-coclear Medial en el Enmascaramiento Contralateral e Interacciones Binaurales: Estudio electrofisiologico en conejillos de Indias

Contralateral broadband noise (BBN) elevates ipsilateral auditory thresholds (central masking) and reduces the amplitude of ipsilateral brainstem auditory evoked potentials (BAEPs). Binaural interactions are complex psychophysical phenomena, but binaural interaction components are easily extracted from BAEPs to monaural versus binaural click stimulation. However, contralateral, or binaural, acoustical stimulation is known to activate simultaneously the crossed and uncrossed medial olivocochlear (MOC) efferent systems and decrease activity in both cochleas. Particularly, contralateral BBN stimulation suppresses in part ipsilateral peripheral activity. What is the role of such contralateral induced peripheral suppression in the overall changes in central BAEPs observed during contralateral masking or binaural stimulation? Compound action potentials (CAPs) of the auditory nerve and BAEPs were recorded simultaneously in awake guinea pigs from electrodes chronically implanted on the round window of the cochlea and the surface of the brain. Peripheral and central measures of contralateral masking and binaural interactions were obtained from responses to monaural or binaural clicks, with or without contralateral BBN, recorded before, during, and after the reversible blockade of the MOC function following a single intramuscular injection of gentamicin. Contralateral BBN effectively reduced the amplitudes of CAP and of all BAEP peaks. CAP to ipsilateral click did not, however, change significantly from monaural to binaural click stimulation; still, normal binaural interaction components developed in the BAEPs. When the medial efferent function was blocked by gentamicin, the normal contralateral BBN suppression of CAP and of the earliest BAEP peak was lost; however, the later BAEP peaks were suppressed by contralateral BBN as before gentamicin, and the central binaural interaction components were unchanged. In these experimental conditions, the MOC efferent system seems to play little role in centrally recorded contralateral masking and binaural interactions. Sumario El ruido de banda ancha (BBN) eleva los umbrales auditivos ipsilaterales (enmascaramiento central) y reduce la amplitud de los potenciales auditivos evo-cados (BAEPs) ipsilaterales. La interacción es un fenómeno psicofísico complejo, pero los componentes de interacción binaural pueden ser extraídos fácilmente de los BAEPs al estimular con clicks uno vs ambos oídos. Sin embargo, se sabe que la estimulación acústica contralateral y la binaural activan simultáneamente el sistema olivo-coclear medial (MOC) cruzado o ipsilateral y disminuyen la activi-dad de las dos cócleas. La estimulación con BBN particularmente suprime en parte la actividad per-iférica Cuál sería el papel de esa supresión per-iférica inducida, en los cambios en los BAEPs centrales observados durante el enmascaramiento contralateral o la estimulación binaural? Se regis-traron simultáneamente los componentes de los potenciales de acción (CAPs) del nervio auditivo y los BAEPs en conejillos de Indias despiertos a través de electrodos implantados en la ventana redonda y en la superficie del cerebro. Se obtuvieron mediciones del enmascaramiento contralateral periférico y central y de las interacciones binaurales ante estímulos mono o binaurales con clicks, con o sin BBN contralateral; antes durante o después del bloqueo reversible de la función del MOC con una aplicación única intramuscular de Gentamicina. El BBN contralateral redujo la amplitud de los CAPs y de todos los picos de BAEPs. Los CAPs con clicks ipsilaterales no se modificaron significativamente al estimular con clicks monoaurales o binaurales, pero si desarrollaron componentes de interacción binaural en los BAEPs. Cuando se bloqueó la función eferente medial con Gentamicina se perdió tanto la supresión de los CAPs contralaterales con BBN, como los picos iniciales de los BAEPs; sin emabargo, se suprimieron los BAEPs tardfos con BBN contralateral como antes de la Gentamicina y los componentes de la interacción binaural central permaneció sin cambios. En estas condiciones experimentales, el MOC parece tener un papel mínimo en el enmascaramiento central y en las interacciones binaurales.

Ototoxicity of teicoplanin in the guinea pig

Experiments were performed on guinea pigs to assess the eventual ototoxic side effects of a new glycopeptide antibiotic called teicoplanin. For a better validation, in the same study other animals were treated with tobramycin, a well known ototoxic antibiotic of the aminoglycoside family, and a group of control animals was also constituted. Antibiotic treated animals were injected with the high dose of 90 mg/kg/day during 21 consecutive days. Electrophysiological measures of equilibrium and acoustic functions were taken and morphological evaluations of the cochleas were performed. The results indicate that in these animal experiments teicomycin appears to be clearly toxic for the vestibule and the cochlea.