Changes In Auditory Function Research Articles

Supplemental iron exacerbates aminoglycoside ototoxicity in vivo

There is increasing evidence to suggest that free radical generation is central to a variety of pathological processes, including drug toxicity. Studies demonstrating the ability of gentamicin to facilitate the generation of radical species suggest that this process plays an important role in aminoglycoside-induced ototoxicity. Because transition metals, particularly iron, play an important role in the production of free radicals and the generation of reactive oxygen species, we sought to determine whether gentamicin-induced ototoxicity is exacerbated by increases in serum iron levels. To this end, we assessed the effects of supplemental iron administration (2 mg/kg/day and 6 mg/kg/day) on changes in auditory function induced by co-administration of gentamicin (100 mg/kg/day for 30 days). Experiments were carried out on pigmented guinea pigs initially weighing 250–300 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every third day throughout the treatment period by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving iron in combination with gentamicin demonstrated a more rapid and profound elevation in CAP thresholds compared with animals receiving gentamicin alone. This effect occurred in a dose-dependant manner. Animals receiving supplemental iron alone maintained normal CAP thresholds throughout the treatment period. There was no statistically significant difference in serum gentamicin levels between groups receiving gentamicin alone or gentamicin plus iron. These results provide further evidence of the recently reported intrinsic role of iron in aminoglycoside ototoxicity, and highlight a potential risk of aminoglycoside administration in patients with elevated serum iron.

Iron deficiency anemia and hearing.

Iron deficiency anemia is a frequently occurring clinical disorder. Despite the suggested association with hearing loss in the literature, cochlear sequelae of iron deficiency have yielded conflicting results in experimental studies. Auditory function was tested in iron-deficient and normal male Wistar albino rats using distortion product otoacoustic emissions and auditory brainstem response audiometry for the clarification of the opposing results in the literature. Hemoglobin, hematocrit, serum iron and albumin levels were monitored to verify iron deficiency. Although dramatic differences in weight gain and blood test parameters were noted, no significant change in auditory function due to iron deficiency was detected.

Blockade of opioid-induced changes in auditory function at the level of the cochlea.

We have previously investigated the auditory neural effects of the kappa-opioid receptor agonist, (-)pentazocine. When administered intravenously (i.v.), this drug temporarily alters auditory nerve compound action potential (CAP) amplitudes. To test the hypothesis that the observed neural effects of i.v. (-)pentazocine occur via kappa-receptor interactions within the cochlea, we attempted to block these effects by employing a specific kappa-opioid receptor antagonist applied directly to the cochlear round window (RW) membrane. In 31 normal-hearing, male pigmented chinchillas, amplitude changes in the click-evoked auditory CAP (N1) were tracked at six stimulus intensities during a baseline and a postbaseline period in which i.v. (-)pentazocine (8 mg/kg) was administered. (-)Pentazocine administration was preceded by the delivery to the cochlear RW membrane of an artificial perilymph solution given alone or containing the kappa-opioid receptor selective antagonist, norbinaltorphimine (Nor-BNI), which was administered at two concentrations in separate groups of animals. The amplitude increase in the CAP after (-)pentazocine was significantly reduced when i.v. (-)pentazocine was preceded by RW-administered Nor-BNI (4 mM). The reversibility of agonist effects by Nor-BNI indicates direct or indirect opioid kappa-receptor-mediated auditory neural effects at the level of the cochlea and suggests a connection between kappa-receptors and auditory neural function.

Ontogeny of hearing in the marsupial, Monodelphis domestica, as revealed by brainstem auditory evoked potentials

Auditory development was studied in the Brazilian short-tailed opossum, Monodelphis domestica, using the brainstem auditory, evoked potential (BAEP). Consistent responses can first be recorded 29 days after birth. The hearing range at the onset of hearing is limited to 5–20 kHz with lowest thresholds of 60 dB SPL at 8–12 kHz. During ontogeny, the hearing range expands towards lower and higher frequencies and thresholds decrease until the adult audiogram is obtained by about day 40. Peak latencies and central conduction times are very long at the onset of hearing and decrease until about day 37. In Monodelphis, ontogenetic changes of auditory function are in good agreement with those described for eutherian mammals, suggesting that this small marsupial species can be used as a general model system for auditory development in mammals.

Neurotransmitters and neuromodulators of the mammalian cochlea.

Major topics addressed in this review on neurotransmitters and neuromodulators of the mammalian cochlea are ; 2) neuronal circuity of the organ of Corti ; 2) hair cell neurotransmitter(s) ; efferent neurotransmitters and neuromodulators (acetylcholine, γ-aminobutyric acid, dopamine, enkephalins, dynorphins, calcitonin gene-related peptide, excitatory amino acids ; and 3) other neuroactive substances in the cochlea (adenosine, ATP, taurine, auditory nerve-activating substance, histamine)

On the pathomechanism of cochlear dysfunction in experimental perilymph fistulas

The mechanism leading to hearing impairment in perilymph fistulas was investigated in guinea pigs with perforated round window membranes (RWM) by analyzing alterations of inner ear fluid pressure, changes of auditory function following manipulations to get presumed air bubbles out of the cochlea ("positional audiometry"), and temporal bone sections. The instantaneous loss of normal positive inner ear fluid pressure after RWM perforation had no immediate effect on auditory function. Inner ear pressure was restored 4 days following RWM perforation. "Positional audiometry" was negative in guinea pigs with perforated RWM. All ears in which auditory thresholds had increased had additional iatrogenic lesions at the spiral lamina. Fistulas in the RWM per se do not affect auditory thresholds. The question of the surgical repair of fistulas was not directly addressed; it only can be concluded that there are no direct sequelae of an isolated fistula which induce auditory impairment and which could be prevented by surgical repair of the fistula.

Subclinical changes of auditory function in the aged

Elderly normal hearing subjects were studied using tests for cochlear functions (remote masking, brief tone audiometry, critical ratio, evoked otoacoustic emission), for neural auditory function (tone decay) and for central auditory functions (ipsilateral vs. contralateral acoustic reflex, tonal masking level difference). The findings demonstrated that ageing can cause subclinical abnormalities, almost consistently localized to the inner ear vibrating structures and only occasionally to the sensory and/or neural elements.

Changes in auditory function associated with 2‐cyano‐butyl‐acrylate adhesive implanted in the middle ear of experimental animals

The effects on auditory function caused by the implantation of 2-cyano-butyl-acrylate adhesive in the middle ear was investigated in experimental animals. Auditory brainstem responses to click stimuli were used to measure hearing thresholds prior to and following implantation of 2-cyano-butyl-acrylate adhesive in the middle ear of guinea pigs. A permanent and deep threshold shift observed at 2 months in 62% of the examined animals, suggested that this tissue adhesive is an ototoxic middle ear implant material and should not be considered in reconstructive middle ear surgery. The functional data correlate well with some of the previous morphological observations.

Recovery of auditory function following intense sound exposure in the neonatal chick

We report the changes in auditory function that occurred at selected intervals following exposure to an intense pure-tone stimulus. One day old chicks were exposed to a 0.9 kHz tone for 48 h at 120 dB. At 0, l, 3, 6, 9, 12 and 15 days after exposure, cochlear nucleus sound-evoked potentials were used to assess threshold sensitivity and frequency selectivity. Immediately after removal from the pure tone a threshold shift of 60 dB relative to age-matched controls was measured. The sharpness of tuning curves, as measured by Q 10 dB. decreased by over 50%. By post-exposure day 15, near complete recovery of function was seen, with the greatest recovery occurring within the first three days. We relate these results to recent reports of structural recovery on the basilar papilla of the chick.

Effects of cocaine on the brain-stem auditory evoked potential in the Long-Evans rat

The present study examined the effects of an acute psychoactive dose of cocaine hydrochloride (HCl) in the rat, using the brain-stem auditory potential (BAEP) as an objective, quantitative measure of this substance's effects on brain and auditory electrophysiology. The animals were 8 adult Long-Evans rats (4 female, 4 male). BAEPs were recorded from skull screw electrodes during a baseline period as well as 30–90 min after cocaine HCl treatment (10 mg/kg, i.p.). Normothermia was maintained to control for possible temperature-related effects. Cocaine's effects on the BAEP were examined over a broad range of stimulus intensities (intensity profiles) and repetition rates (rate profiles). Cocaine prolonged latencies of several BAEP components at low stimulus intensities and shortened these latencies at high stimulus intensities. The average BAEP threshold was alos increased by cocaine treatment. These results were not strong, but were suggestive of a recruitment type change in auditory function. Cocaine treatment had no convincing effects on the BAEP as a function of stimulus repetition rate.

Theophylline-induced changes in the mouse brainstem auditory evoked potential

Because theophylline is a widely used analeptic, there is interest in its possible ototoxic and neurotoxic effects. The present study used the brainstem auditory evoked potential (BAEP) to evaluate the acute effects of theophylline on auditory electrophysiology in mice. Adult female C57BL/6 mice were injected intraperitoneally with 150 mg/kg theophylline or saline. The BAEP thresholds and latency-intensity profiles suggested that theophylline induced a rather slight but statistically significant change in auditory function that was suggestive of a temporary recruitment-type sensorineural deficit. This observation raises concerns about the possible ototoxic effects of theophylline, particularly in asthmatic patients and apneic preterm neonates who receive this drug chronically. While there was BAEP evidence of ototoxic effects for theophylline, there was no evidence of neurotoxic effects.

Effects of temperature and elevated intracranial pressure on peripheral and brain stem auditory responses in dogs

Far-field recordings of central (P2 through P4) and peripheral (cochlear microphonic; and compound action potential of the eighth nerve) auditory responses were used to assess changes in auditory function resulting from elevated intracranial pressure. Normative data for eight dogs were obtained. The relationship between response latency and core temperature was examined. A mean slope of −0.17 ms/°C resulted for the temperature range of 35.0 to 40.0°C. Systemic arterial pressure was measured in order to identify the cerebral ischemic response. Responses were not altered significantly unless the intracranial pressure approached within 15 to 30 mm Hg of mean systemic arterial pressure. Changes in the response consisted of both enhancement and deterioration during intracranial pressure elevation and were accompanied by increases in systemic arterial pressure during that elevation. Supernormal amplitudes of the action potential also occurred during recovery periods. Results suggest that: (i) during elevated intracranial pressure, changes in both central and peripheral auditory function result from ischemia rather than pressure-induced distortion of the cochlea or central neural assemblies. (ii) Far-field auditory responses may include an O 2-dependent cochlear microphonic. (iii) An unknown process causing enhancement of central and peripheral neural responses exists and operates in connection with intracranial hypertension. Possible mechanisms underlying enhancement of response components are discussed.

Original Papers · Travaux originaux: Studies of Normal Hearing

Auditory function changes continually from birth to old age. A variety of methods to assess hearing have evolved since the invention of the audiometer. Types of measurement include: electrical response in the central nervous system, cochlear acuity and speech responses. While some of these tests correlate fairly well with each other, their ability to represent overall hearing function is questionable. Other attempts to improve the assessment of hearing have been made in the area of self-appraisal, but these, too, have significant limitations. Most self-report and peer appraisal questionnaires have been established by studies of hearing-impaired populations. Norms for these techniques in normal-hearing populations need to be established. There is still room for valid tests of everyday communication. What we have in measurement procedures does not achieve this goal. Research studies of today will hopefully produce better definition of normal auditory function.

Comparative toxicity of gentamicin and tobramycin in rats at low multiples of the human therapeutic dose

Previously conducted investigations in rats comparing gentamicin to tobramycin at high multiples of the usual human dose have reported tobramycin to be less nephro- and/or ototoxic than gentamicin. In this study, comparative effects on kidney and hearing/equilibrium between the antibiotics at doses approximating one to three times the daily human therapeutic dose (3 to 5 mg/kg/day) were examined. Gentamicin or tobramycin were given by intramuscular injection to groups of 20 male Sprague-Dawley rats at dose levels of 3, 6, and 9 mg/kg/day for 30 consecutive days. Each rat was tested weekly for changes in auditory function and assessed for effects on vestibular function. Routine clinical laboratory determinations for evaluation of nephrotoxicity were performed throughout the study. Representative portions of the kidney were examined histologically. There were no adverse effects observed on hearing function or equilibrium. Renal responses to the administration of either aminoglycoside included marginal polyuria with a concomitant decrease in urine osmolality at the 6 and 9 mg/kg dose levels. Very mild histomorphological changes of the proximal cortical tubules, typical of an aminoglycoside-induced toxicity, were noted in both drug groups at all dosages. The incidence of these changes was dose-related and was similar between the corresponding aminoglycoside groups. Following single-dose administration, drug serum levels of either antibiotic were similar and compared favorably to those reported in patients receiving gentamicin or tobramycin at usual clinical doses. The results of this study indicate that there were no renal or auditory/vestibular toxicologic differences between gentamicin and tobramycin when given to rats at levels equal to the clinical dose or at low multiples thereof.

Auditory Dysfunction With Facial Paralysis

A series of 58 patients with idiopathic facial paralysis were studied to determine if a concomitant cochlear or eight nerve auditory dysfunction could be identified with traditional audiologic tests. Results indicated that only those patients with a facial nerve lesion, proximal to the stapedius branch, experienced reduced tolerance for loud sounds, reduction of speech discrimination at high-intensity levels, and abnormal loudness growth. Such findings suggest that changes in auditory function, accompanying facial nerve paralysis, are a mechanical effect due to absence of stapedial action. Site of lesion tests in this sample failed to demonstrate eighth nerve dysfunction and, thus, does not support a theory of polyneuropathy that involves the auditory nerve.

Averaged evoked auditory responses in the chronically implanted cat.

AbstractAveraged evoked auditory responses from chronically implanted dural electrodes over the midectosylvian gyrus were evaluated in eight cats. The effects of the distribution of electrodes and levels of alertness were observed for each animal and the entire group. Changes in duration, rise and decay times, and repetition rates were also analyzed. Data from these experiments suggested a large variability in the amplitude and latency of the response. On the other hand, they also suggested a stable reproducible threshold of detectability — a point where the response disappeared upon further reduction in sound pressure levels. This characteristic of the evoked system served as a reliable measurement of an evoked auditory threshold and appeared as a potential means for evaluating relative changes of auditory function within the same animal.

Audiological Aspects of Neuro-Otology: (The present practice at Queen Square)

IntroductionThe evaluation of the patient with vertigo or other sensations of disturbed spacial orientation can be a difficult and perplexing task. But if these complaints are accompanied by changes in auditory function, the differential diagnosis of the disorder is usually made easier for the clinician. Therefore, a careful and systematic analysis of threshold and suprathreshold auditory functions should be a part of the clinical examination of every ‘dizzy’ patient, but it has not been the custom in Queen Square to perform a large number of tests, but to make sure that a few well-tried ones are meticulously carried out. Thus tests of auditory discrimination of complex signals such as speech, detection of the presence of recruitment, alongside pure tone air and bone conduction with adequate masking, are necessary, but the use of over-elaborate audiological testing schemes in clinical practice does much to discredit neuro-otology.The problem of central deafness is, as yet, often difficult to understan. Sm...

Hearing Impairment following Subtotal Electrolytic Lesions to the Auditory-Nerve Region of the Guinea Pig

Guinea pigs were surgically prepared with permanent monopolar recording electrodes and bipolar lesion electrodes placed in the 8th nerve cochlear-nucleus region. Continuous-trace absolute-threshold recordings (visual-detection level) for 1, 50, 100, and 1000 clicks/second were made over 3-min measurement periods by means of a motor-driven recording attenuator. Neural equilibration at suprathreshold levels was evaluated in terms of evoked-potential amplitudes. Following subtotal electrolytic lesions to the nerve, threshold and amplitude changes were monitored regularly over a 13-week period. Parallel data were collected from additional guinea pigs trained to track absolute thresholds to discrete white-noise stimuli by means of an avoidance-conditioning procedure. Changes in auditory function are interpreted in terms of reversible and nonreversible neural damage. [Work supported in part by National Institute of Neurological Diseases and Blindness.]