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Neural adaptation to pulsatile acoustical stimulation in the cochlear nucleus of the rat.

This study, carried out in adult Long-Evans rats, was designed to investigate the adaptive properties of the cochlear nucleus to pulsatile acoustical stimuli. To achieve this purpose, near-field evoked potentials were picked up from the ventral cochlear nucleus in awake animals. Individual auditory thresholds were measured and responses to 250 ms trains of repetitive clicks with pulse rates ranging from 100 to 2000 pulses per second were collected. The amplitude of the first negative (N(1)) component of the evoked potentials to consecutive individual pulses in the train was measured by using a subtraction method. As expected, a rapid amplitude decrement of the responses in the train was obtained and a three phase adaptation was described. The decrease of individual N(1) component amplitude was fitted for each rate of stimulation with exponential decrease equations and time constants were calculated. Such an analysis allowed us to characterize three distinct adaptive processes which were discussed. The results were comparable to those obtained in previous studies in the auditory nerve and suggest that the adaptation recorded in the ventral cochlear nucleus by using near-field evoked potentials reflects the adaptive properties of auditory nerve fibers.

Acoustic Stimulation↗

The echolocation calls of the spotted bat Euderma maculatum are relatively inaudible to moths

Previous studies of the spotted bat Euderma maculatum have demonstrated that this bat emits echolocation calls that are lower in frequency, shorter in duration and fainter in intensity compared with those of most other insectivorous bats, acoustic characteristics which should render it less conspicuous to eared moths. We tested this prediction by monitoring electrophysiologically the ears of sympatric noctuoid (noctuid, arctiid and notodontid) moths in a site in western Canada. Auditory threshold curves demonstrate that most of the moths tested are less responsive to the calls of Eu. maculatum than to those of another sympatric bat, Eptesicus fuscus. Playbacks to moth ears of pre-recorded search- and approach-phase echolocation calls of Eu. maculatum and Ep. fuscus further demonstrate that the calls of Eu. maculatum are poorly detectable to moths and, in some cases, completely inaudible. We estimate that, in the wild, an average noctuoid moth would detect the calls of Eu. maculatum at distances of less than 1 m as opposed to the calls of Ep. fuscus which should be first heard at distances of 20­25 m. Although most moths are unable to adequately hear Eu. maculatum, the observation that two individuals possessed ears sensitive to this bat's calls suggests the existence of auditory pre-adaptation to this type of echolocation.

Journal Article↗

[The effects of iron supplementation on auditory brain-stem response with iron deficiency anemia in rats].

OBJECTIVE: To evaluate the therapeutic methods of sensorineural hearing loss with iron deficiency anemia and their effects. METHOD: Sixty-eight Wistar rats were randomly divided into 3 groups: Group A (iron deficiency group A) 24 rats, group B (iron deficiency group B) 24 rats and group C (control group) 20 rats. Group A and B were fed with iron deficiency diet for 6 weeks. By analyzing ABR and DPOAE, hearing loss was detected in group A and B. Then, group A was given iron supplementation diet and hyperbaric oxygen therapies, and group B was given iron supplementation diet only. RESULT: The auditory thresholds and period latencies (PL) of I waves of ABR and DPOAE amplitude in 2 kHz and 3 kHz within group A and B were significantly different before and after treatment (P < 0.05). But the effects of treatment between these two groups had not significant differences (P > 0.05). CONCLUSION: It suggested that good results can be obtained by early iron supplementation in iron deficiency hearing loss cases. Hyperbaric Oxygen therapy may not be necessary.

Anemia, Iron-Deficiency↗

Frequency-specific aspects of the auditory brainstem response threshold elicited by 1000-Hz filtered clicks in subjects with sloping cochlear hearing losses.

The frequency specificity of the ABR threshold evoked by a 1000-Hz filtered click was determined in subjects with sloping cochlear hearing losses, both high- and low-frequency in character. The results show that the ABR threshold evoked by this stimulus is low-frequency specific. The standard error in estimating the 1000-Hz pure-tone threshold (PTT) is 10.4 dB, which equals that for estimating the 3000-Hz PTT from the routinely used click-evoked ABR threshold. The ABR threshold evoked by a 1000-Hz filtered click can therefore be regarded as an accurate tool to predict the pure-tone hearing loss at 1000-Hz. In comparison with the ABR threshold evoked by a click masked with 1590-Hz high-pass noise, the ABR threshold evoked by a 1000-Hz filtered click has a larger dynamic range, yields a larger number of useful responses and is less time consuming. For clinical low-frequency-specific ABR threshold assessment, the 1000-Hz filtered click is therefore preeminently useful.

Adolescent↗

Kanamycin induced ototoxicity in the laboratory rat. A comparative morphological and audiometric study.

Two comparative experiments on the behavioural, audiometric and histological effects of kanamycin-induced cochleotoxicity in the Wistar rat are reported. In the first experiment kanamycin 400-1,500 mg/kg/day was injected subcutaneously for 20 days and the morphological damage to the organ of Corti assessed. In the second experiment the progression of damage to the organ of Corti was examined in animals given kanamycin 700 mg/kg/day for 4-20 days. Behavioural audiometric studies of threshold shift were undertaken throughout both experiments. In the first study, all the animals were killed after a recovery period of 20 days from the last injection, i.e., day 40, and in the second study groups of animals were killed at 4-day intervals between days 4 and 20 of dosing. One cochlea from each animal was critical point-dried, dissected to expose the organ of Corti and examined by scanning electron microscopy. A vertical section through the contralateral cochlea was examined by light microscopy. The results of the morphological examination of the cochleas were collated with the behavioural audiometry. The morphological damage to the organ of Corti followed a stereotyped pattern of degeneration, the extent of which appeared to be determined both by the number and concentration of the kanamycin administrations. The collateral audiometric examinations indicated that extensive damage had taken place before a shift in the behavioural auditory threshold could be detected by observation of the Preyer reflex.

Animals↗

[Identification of the waveform of cortical auditory evoked potentials].

Slow vertex response (SVR) audiometry is presently one of the methods of choice in objective auditory threshold assessment. The aim of this study, carried out on twenty subjects with various degrees and types of hearing loss, was to evaluate the difficulties found in N1P2 complex identification. Tracings, presented as single averages and super-imposed averages, were examined separately by two Authors who had not been received any information concerning the audiometric thresholds of the subjects under investigation. Results showed that erroneous identification of SVR waveforms occurred frequently, especially near threshold level. The rate of false negatives (i.e. a waveform present but not identified) was higher than the rate of false positives (i.e. erroneous identification of a non-existing N1P2 complex). High intra- and interindividual discrepancies were also found. Our results appear to indicate that the SVR waveform is not easily identifiable and thus that SVR audiometry cannot, therefore, be considered a truly objective audiometric test since analysis of the tracings may be influenced by the high degree of variability in individual interpretation.

Adolescent↗

Glucocorticoid impact on cochlear function and systemic side effects in autoimmune C3.MRL-Faslpr and normal C3H/HeJ mice.

Glucocorticoids are effective in reversing hearing loss, but their severe side effects limit long term management of many ear disorders. A clearer understanding of these side effects is critical for prolonged therapeutic control of hearing and vestibular dysfunction. Therefore, this study characterized the impact of the glucocorticoid prednisolone on cochlear dysfunction and systemic organ systems in C3.MRL-Fas(lpr) autoimmune mice and their normal C3H/HeJ parent strain. Following 3 months of treatment, autoimmune mice had better auditory thresholds and improved hematocrits, anti-nuclear antibodies, and immune complexes. Steroid treatment also lowered body and spleen weights, both of which rise with systemic autoimmune disease. Steroid treatment of the normal C3H/HeJ mice significantly elevated their blood hematocrits and lowered their body and spleen weights to abnormal levels. Thus, systemic autoimmune disease and its related hearing loss in C3.MRL-Fas(lpr) mice are steroid-responsive, but normal hemopoiesis and organ functions can be significantly compromised. This mouse model may be useful for studies of the detrimental side effects of steroid treatments for hearing loss.

Animals↗

The effects of leupeptin on cochlear blood flow, auditory sensitivity, and histology.

The purpose of this study was to evaluate the long-term safety of administering leupeptin (1 mg/ml in Hank's Balanced Salt Solution) to the round window membrane by investigating its effects on cochlear blood flow, auditory sensitivity (i.e., auditory brainstem response), and cochlear histology. A comparison of baseline and posttreatment measurements of cochlear blood flow and mean arterial blood pressure in guinea pigs revealed no significant changes. Auditory brainstem response measurements revealed no significant changes in auditory threshold shifts when compared to controls at the 2-, 4-, 6-, and 8-week time points. Furthermore, poststudy surface preparations of the organs of Corti and cytocochleograms from leupeptin-treated ears and controls revealed no significant hair cell losses. These data suggest that the prolonged administration of leupeptin (1 mg/ml at a rate of 0.5 microliter/hr for 8 weeks) to the round window membrane is not ototoxic. This study may serve as a basis for future clinical trials of leupeptin administration for the prevention or treatment of noise-induced hearing loss and the management of tinnitus.

Animals↗

Developmental course of brain-stem auditory evoked potentials in the first days of full term infants.

Modifications of brain-stem acoustic evoked potentials (BAEPs) in the first 5 days of life of normal full-term infants are reported. BAEPs were recorded using rarefaction clicks at 70, 60, 40, 20 dB HL. Multiple linear regression analysis was performed to evaluate chronological and gestational age differences for all positive and negative peaks, interpeak latencies, amplitudes and amplitude ratios. The percentage of newborn infants with auditory threshold of 20 dB HL increased with the number of days. At all intensities the latency of PIII and PV decreased significantly between the 2nd and 3rd day, while the latency of PI decreased significantly between the 3rd and the 4th day; PIII and PV latencies decreased also between the 4th and the 5th day. The longer the period of gestation the longer was the PI latency recorded between the 2nd and 5th day after birth. The anatomical and physiological changes developing shortly after birth are probably responsible for the above findings. These changes most probably appear firstly in the cochlear and trapezoid nuclei and later on in the organ of Corti.

Age Factors↗

Developmental exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107): long-term effects on brain development, behavior, and brain stem auditory evoked potentials in rats.

In the present study the developmental neurotoxic effects of the PCB metabolite 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) were compared with effects caused by a mixture of parent polychlorinated biphenyl (PCB) congeners (Aroclor 1254). Pregnant female Wistar rats were exposed to 0.5 or 5 mg 4-OH-CB107, or 25 mg Aroclor 1254 per kg body weight from gestation days 10 to 16. Plasma thyroid hormone levels were significantly decreased in the offspring of all treatment groups at postnatal day 4 (PND 4). Behavioral experiments using an open field paradigm revealed an impaired habituation in male offspring of all treatment groups at PND 130. Passive avoidance experiments indicated significant influences on the time course of step-down latencies across trials in exposed male rats. Catalepsy induced by haloperidol showed increases in latencies to movement onset in female offspring exposed to 0.5 mg 4-OH-CB107 compared to Aroclor 1254 treated offspring at PND 168-175. Male offspring exposed to 4-OH-CB107 or Aroclor 1254 showed decreases in latencies compared to control animals. Brain stem auditory evoked potentials (BAEPs) measured at PND 300-310 showed significant increases in auditory thresholds in the low frequency range between Aroclor 1254 and 4-OH-CB107 (5 mg/kg bw) treated animals. Measurements of neurotransmitter levels revealed effects of Aroclor 154 exposure on both the dopaminergic and the serotonergic systems, whereas 4-OH-CB107 exposure affected dopaminergic and noradrenergic systems, with slight but not significant effects on the serotonergic system. These results indicate that 4-OH-CB107 is able to induce long-term effects on behavior and neurodevelopment. The observed effects for 4-OH-CB107 are similar to, but in some aspects different from, the effects observed after Aroclor 1254 exposure.

Animals↗

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

Action Potentials↗

Contribution to the differentiation of peripheral versus central tinnitus via auditory brain stem response evaluation.

Auditory brain stem response (ABR) parameters were evaluated in 54 subjects with unilateral idiopathic subjective tinnitus in order to verify the possibility of detecting its site of origin. All the subjects had normal hearing or a symmetrical bilateral sensorineural hearing loss. All the cases in whom middle or inner ear disease had been diagnosed, were excluded. Subjects, classified on the basis of their mean auditory threshold and masking curves according to Feldmann, underwent a residual inhibition (RI) test and ipsilateral narrow-band noise masking before a second ABR test was performed. Patients with positive RI made up the A+ group, while those with negative RI made up the A- group. The main characteristics observed were an increase of the mean latency values of wave I in the tinnitus ear in the A+ group while, after masking, the values of the affected and unaffected ears almost overlapped. An increase in the latency values of wave V, unaffected by the masking procedure, could be observed in A- patients. The occurrence of waves I and III was often affected in the tinnitus ears in both groups, but it increased, after masking, only in the A- patients. Based on the obtained data, the authors conclude that there may be a substantial difference concerning ABR parameters between the patients in whom residual tinnitus masking is demonstrable compared with those in whom it is not.

Adult↗

Differential susceptibility of rats and guinea pigs to the ototoxic effects of ethyl benzene.

The present study was designed to compare the ototoxic effects of volatile ethyl benzene in guinea pigs and rats. Rats showed deteriorated auditory thresholds in the mid-frequency range, based on electrocochleography, after 550-ppm ethyl benzene (8 h/day, 5 days). Outer hair cell (OHC) loss was found in the corresponding cochlear regions. In contrast, guinea pigs showed no threshold shifts and no OHC loss after exposure to much higher ethyl benzene levels (2500 ppm, 6 h/day, 5 days). Subsequently, a limited study (four rats and four guinea pigs) was performed in an attempt to understand these differences in susceptibility. Ethyl benzene concentration in blood was determined in both species after exposure to 500-ppm ethyl benzene (8 h/day, 3 days). At the end of the first day, blood of the rats contained 23.2+/-0.8-microg/ml ethyl benzene, whereas the concentration in guinea pig blood was 2.8+/-0.1 microg/ml. After 3 days, the concentration in both species decreased with respect to the first day, but the ethyl benzene concentration in rat blood was still 4.3 times higher than that in guinea pig blood. Thus, the difference in susceptibility between the species may be related to the ethyl benzene concentration in blood.

Acoustic Stimulation↗

Prevention of noise- and drug-induced hearing loss with D-methionine.

A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating D-methionine (D-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented D-met's otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further D-met has an excellent safety profile. D-met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in D-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral D-met protection against cisplatin-induced ototoxicity, D-met protection against amikacin-induced ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.

Amikacin↗

Auditory brainstem response thresholds in a mouse mutant with selective outer hair cell loss.

Mutant animals with a particular type of cochlear pathology are an excellent model for studying the functional role of various cells of the cochlea. In homozygous WV/WV mutant mice we found a selective loss of outer hair cells as a constant defect with no progressive degeneration of the organ of Corti. The mice were followed throughout their lives and exhibited auditory brainstem responses that were elevated to about 50 dB SPL as compared to normal control animals. Sequential temporal bone studies showed that there was a selective loss of outer hair cells throughout the entire cochlea as seen in surface preparations. The inner hair cells were present in normal numbers and appeared to be essentially normal.

Aging↗

Persistent stress-induced sensitization of adrenocortical and startle responses.

We assessed the functional adrenocortical and behavioral state of rats previously exposed to repeated stressor presentations. In Experiment 1, the whole-body startle response to threshold (91 dB) and suprathreshold (96 dB) stimuli was assessed in rats given 3 daily sessions (3DS) of 40, 2-mA tailshocks. The 3DS rats showed an exaggerated startle response to the threshold auditory stimulus 4 days poststressor compared to nonshocked controls (CON). An exaggerated startle response in stressed rats was not evident either 1 day or 10 days poststressor. In Experiment 2, adrenocortical sensitization and behavioral reactivity were assessed in rats exposed to 1 day (1DS) or 3 days of our stress regimen. Stressed rats exhibited elevated basal plasma corticosterone (CORT) levels 1 day poststressor which recovered by 9 days poststressor. Stressed rats also exhibited suppressed open-field activity 4 days poststressor. On the 10th day poststressor, rats were exposed to a single tailshock. The 1DS and 3DS rats showed both a sensitized and prolonged CORT response to stressor reexposure compared to control rats which received only the single tailshock. In addition, on the 11th day poststressor 3DS rats exhibited a moderate recapitulation of the elevated basal CORT levels seen after the initial stressor exposures. Thus, exposure to our stress regimen produces a chronic stress state in rats characterized by persistent behavioral and adrenocortical sensitization, as well as suppressed open-field activity and elevated basal CORT levels. Rats exhibiting a chronic stress state may be appropriate as a model for the study of stress-related psychophysiological illnesses, such as posttraumatic stress disorder.

Acoustic Stimulation↗