Electrocochleography and experimentally induced loudness recruitment

The relationship between changes in loudness and the cochlear whole-nerve potential following experimentally produced deafness was studied in an animal model. Reaction time of a subject's response to an auditory stimulus has been shown to be an index of loudness in human experiments and has been adapted to nonhuman primates. In a series of experiments, four macaque monkeys were operantly conditioned to respond to 8-kHz tones over a range of 3--80 dB SPL, and their reaction times to pure tone stimuli were measured. Whole-nerve cochlear action potentials were recorded from chronic inner-ear electrodes. The relationship between behavioral and electrical measures of loudness recruitment were examined in animals with both temporary and permanent noise-induced hearing loss. Loudness recruitment was demonstrated experimentally after a 1-h exposure to a high-intensity 8-kHz octave band of noise. Excellent agreement was observed between the reaction time function and the action potential input-output function at intervals of 0.5, 12, 24, 48, and 84 h after exposure. Permanent hearing loss was produced in some of these animals by a much longer duration of exposure to the 8-kHz octave band of noise. Recruitment was observed in both the behavioral and the electrical measures. Histological studies of these damaged cochleas revealed primarily outer hair cell destruction, with a relative sparing of inner hair cells and nerve supply. The findings of this study are interpreted as strong support for the clinical electrocochleogram as an objective indicator of the presence of loudness recruitment.     

Hearing loss and cochlear pathology in the monkey (Macaca) following exposure to high levels of noise

Summary Eight Old World monkeys were exposed 8 h daily for 20 days to octave-band noise having center frequencies from 0.5–8 kHz at levels of 117–120 dB SPL. Two additional animals received exposures to wide-band, 120-dB SPL noise on the same schedule, and one animal was exposed to the 2-kHz octave band for 40 h continuously. Behavioral audiograms were measured throughout exposure and during a 1-month recovery period. Following recovery, the animals were sacrificed and their ears examined histologically. Monaural audiograms are presented showing initial and final TTS and PTS measured at the end of the recovery period. These are compared with complete cytocochleograms for each ear. Hair cell loss was generally restricted to the outer rows, and was reasonably well correlated with pattern of hearing loss. Some cell loss, including inner hair cells, was found in the extreme basal turn, usually without associated high-frequency hearing loss. The relationships between exposure frequency, hearing loss, and locus of cochlear pathology are discussed, as are changes in TTS during exposure.This investigation was supported by research grants NS-05077, NS-05065 and NS-12706 and by Program Project grant NS-05785 from the National Institutes of Health     

Effects of intense noise exposure on the outer hair cell plasma membrane fluidity

Outer hair cells (OHCs) play an important role in cochlear amplification via their length changes (electromotility). A noise-induced cochlear amplification loss leading to a permanent threshold shift (PTS) was observed without a significant hair cell loss in rats [Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1-9.]. Since motor proteins are inserted in the OHC lateral membrane, any change in the OHC plasma membrane may result in a loss of OHC electromotility, leading to a loss of cochlear amplification. In this study, the lateral diffusion in the OHC plasma membrane was determined in vitro in guinea pigs by fluorescent recovery after photobleaching (FRAP) after an in vivo noise exposure. The lateral diffusion in the OHC plasma membrane demonstrated a length-dependence, which increased as OHC length increased. A reduction in the lateral diffusion was observed in those OHCs with lengths of 50-70 microm after exposure to an 8-kHz octave band noise at 110 dB SPL for 3h. This membrane fluidity change was associated with the selective PTS at frequencies around 8 kHz. The reduction of the lateral diffusion in the OHC lateral wall indicated that noise could impair the micromechanics of the OHC lateral wall and might consequently impair OHC electromotility to induce threshold shift.     

Hearing loss and cochlear pathology in the monkey (Macaca) following exposure to high levels of noise.

Eight Old World monkeys were exposed 8 h daily for 20 days to octave-band noise having center frequencies from 0.5--8 kHz at levels of 117--120 dB SPL. Two additional animals received exposures to wide-band, 120-dB SPL noise on the same schedule, and one animal was exposed to the 2-kHz octave band for 40 h continuously. Behavioral audiograms were measured throughout exposure and during a 1-month recovery period. Following recovery, the animals were sacrificed and their ears examined histologically. Monaural audiograms are presented showing initial and final TTS and PTS measured at the end of the recovery period. These are compared with complete cytocochleograms for each ear. Hair cell loss was generally restricted to the outer rows, and was reasonably well correlated with pattern of hearing loss. Some cell loss, including inner hair cells, was found in the extreme basal turn, usually without associated high-frequency hearing loss. The relationships between exposure frequency, hearing loss, and locus of cochlear pathology are discussed, as are changes in TTS during exposure.     

Candidate's thesis: enhancing intrinsic cochlear stress defenses to reduce noise-induced hearing loss

OBJECTIVES/HYPOTHESIS: Oxidative stress plays a substantial role in the genesis of noise-induced cochlear injury that causes permanent hearing loss. We present the results of three different approaches to enhance intrinsic cochlear defense mechanisms against oxidative stress. This article explores, through the following set of hypotheses, some of the postulated causes of noise-induced cochlear oxidative stress (NICOS) and how noise-induced cochlear damage may be reduced pharmacologically. 1) NICOS is in part related to defects in mitochondrial bioenergetics and biogenesis. Therefore, NICOS can be reduced by acetyl-L carnitine (ALCAR), an endogenous mitochondrial membrane compound that helps maintain mitochondrial bioenergetics and biogenesis in the face of oxidative stress. 2) A contributing factor in NICOS injury is glutamate excitotoxicity, which can be reduced by antagonizing the action of cochlear -methyl-D-aspartate (NMDA) receptors using carbamathione, which acts as a glutamate antagonist. 3) Noise-induced hearing loss (NIHL) may be characterized as a cochlear-reduced glutathione (GSH) deficiency state; therefore, strategies to enhance cochlear GSH levels may reduce noise-induced cochlear injury. The objective of this study was to document the reduction in noise-induced hearing and hair cell loss, following application of ALCAR, carbamathione, and a GSH repletion drug D-methionine (MET), to a model of noise-induced hearing loss. STUDY DESIGN: This was a prospective, blinded observer study using the above-listed agents as modulators of the noise-induced cochlear injury response in the species chinchilla langier. METHODS: Adult chinchilla langier had baseline-hearing thresholds determined by auditory brainstem response (ABR) recording. The animals then received injections of saline or saline plus active experimental compound starting before and continuing after a 6-hour 105 dB SPL continuous 4-kHz octave band noise exposure. ABRs were obtained immediately after noise exposure and weekly for 3 weeks. After euthanization, cochlear hair cell counts were obtained and analyzed. RESULTS ALCAR administration reduced noise-induced threshold shifts. Three weeks after noise exposure, no threshold shift at 2 to 4 kHz and <10 dB threshold shifts were seen at 6 to 8 kHz in ALCAR-treated animals compared with 30 to 35 dB in control animals. ALCAR treatment reduced both inner and outer hair cell loss. OHC loss averaged <10% for the 4- to 10-kHz region in ALCAR-treated animals and 60% in saline-injected-noise-exposed control animals. Noise-induced threshold shifts were also reduced in carbamathione-treated animals. At 3 weeks, threshold shifts averaged 15 dB or less at all frequencies in treated animals and 30 to 35 dB in control animals. Averaged OHC losses were 30% to 40% in carbamathione-treated animals and 60% in control animals. IHC losses were 5% in the 4- to 10-kHz region in treated animals and 10% to 20% in control animals. MET administration reduced noise-induced threshold shifts. ANOVA revealed a significant difference (P <.001). Mean OHC and IHC losses were also significantly reduced (P <.001). CONCLUSIONS: These data lend further support to the growing body of evidence that oxidative stress, generated in part by glutamate excitotoxicity, impaired mitochondrial function and GSH depletion causes cochlear injury induced by noise. Enhancing the cellular oxidative stress defense pathways in the cochlea eliminates noise-induced cochlear injury. The data also suggest strategies for therapeutic intervention to reduce NIHL clinically.     

Critical bandwidth in patients with acoustic neuroma

Eleven patients with verified acoustic neuroma had critical band estimation performed by the method of loudness summation using noise bands centered around 1 kHz. The normal loudness difference between broad band noise and narrow band noise was reduced at all levels except the highest. Judged as single individuals, 9 of the 11 patients had a normal critical band. The pooled data indicated a normal critical band, both in patients with hearing loss less than 50 dB HL and in patients with hearing loss greater than or equal to 50 dB HL. The results are similar to those obtained in patients with Ménière's disease (Bonding, 1978c) and thus CB-measurements cannot be utilized for differentiating between cochlear and retrocochlear lesions. However, at the highest test levels applied the loudness difference between broad band noise and narrow band noise appeared to have some correlation to the presence or absence of recruitment.     

Hearing thresholds with outer and inner hair cell loss

Hearing impairment and related cochlear histopathologic changes were evaluated in experimental animals after treatment with aminoglycoside antibiotics or exposure to intense sound. In the course of treatment with kanamycin, neomycin, or dihydrostreptomycin, permanent hearing loss in monkeys and guinea pigs occurred first at the high frequencies and progressed toward the lows. Exposure to different octave bands of noise at 120 dB SPL in monkeys and chinchillas produced permanent hearing loss at frequencies related to the spectral characteristics of the octave band. In most instances loss of outer hair cells was substantially greater than that of inner hair cells. In fact, the pattern and location of missing outer hair cells on the basilar membrane were most often correlated with threshold shifts of 50 dB or less. Generally inner hair cell loss was observed when the threshold shift was greater than 50 dB. Our data support the place principle and the inference that the outer hair cells are essential for hearing from threshold to about 50 dB SL. The inner hair cells, if functioning normally, apparently take over above that level. Although there is little doubt that such a generalization will, in the long term, be found to have been greatly oversimplified, there is every reason to believe that a combination of behavioral and morphologic procedures, as used in this study, will play an important part in elucidating the differences in functional significance of the two types of hair cells.     

Degeneration in the cochlea after noise damage: primary versus secondary events

PURPOSE: To determine if noise damage in the organ of Corti is different in the low- and high-frequency regions of the cochlea. MATERIALS AND METHODS: Chinchillas were exposed for 2 to 432 days to a 0.5 (low-frequency) or 4 kHz (high-frequency) octave band of noise at 47 to 95 dB sound pressure level. Auditory thresholds were determined before, during, and after the noise exposure. The cochleas were examined microscopically as plastic-embedded flat preparations. Missing cells were counted, and the sequence of degeneration was determined as a function of recovery time (0-30 days). RESULTS: With high-frequency noise, primary damage began as small focal losses of outer hair cells in the 4-8 kHz region. With continued exposure, damage progressed to involve loss of an entire segment of the organ of Corti, along with adjacent myelinated nerve fibers. Much of the latter loss is secondary to the intermixing of cochlear fluids through the damaged reticular lamina. With low-frequency noise, primary damage appeared as outer hair cell loss scattered over a broad area in the apex. With continued exposure, additional apical outer hair cells degenerated, while supporting cells, inner hair cells, and nerve fibers remained intact. Continued exposure to low-frequency noise also resulted in focal lesions in the basal cochlea that were indistinguishable from those resulting from exposure to high-frequency noise. CONCLUSIONS: The patterns of cochlear damage and their relation to functional measures of hearing in noise-exposed chinchillas are similar to those seen in noise-exposed humans. Thus, the chinchilla is an excellent model for studying noise effects, with the long-term goal of identifying ways to limit noise-induced hearing loss in humans.     

Combined effects of noise and styrene exposure on hearing function in the rat

Combined exposure to both noise and aromatic solvents such as styrene is common in many industries. In order to study the combined effects of simultaneous exposure to both noise and styrene on hearing, male adult Long-Evans rats were exposed either to 750 ppm styrene alone, to a 97 dB SPL octave band of noise centered at 8 kHz, or to a combination of noise and styrene. The exposure duration was 6 h/day, 5 days/week, for 4 consecutive weeks. Auditory function was tested over a frequency range from 2 to 32 kHz by recording near field potentials from the inferior colliculus, whereas histopathological analyses of the cochleae were performed with conventional morphometric approaches. Whereas both noise and styrene each caused permanent threshold shifts, the mechanisms of cochlear damage were different. Noise-induced hearing loss was mainly related to injuries of the stereocilia, whereas styrene-induced hearing loss was related to outer hair cell losses. Following the combined exposure, the threshold elevations as well as the cell losses exceeded the summed loss caused by noise and by styrene alone in the range of 8-16 kHz. Therefore, these results suggest that the two ototoxicants can cause a permanent synergistic loss of auditory sensitivity.     

水杨酸钠对噪声性听力损失影响的实验

目的 观察水杨酸钠能否减轻噪声引起的听力损失。方法 将３６只健康且耳廓反射正常的花色豚鼠随机分为水杨酸钠实验组、生理盐水对照组、水杨酸钠对照组和噪声暴露组。噪声暴露采用１０５ｄＢ ＳＰＬ的４ＫＨｚ窄带噪声下暴露２ｈ,连续５ｄ。水杨酸钠给药为每天０．５ｇ／ｋｇ体重连续１０ｄ。由短声诱发听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓｅ,ＡＢＲ）,连续测试其阈值;而后取动物双侧耳蜗荧     

Glial cell line-derived neurotrophic factor has a dose dependent influence on noise-induced hearing loss in the guinea pig cochlea

We examined the effectiveness of glial cell line-derived neurotrophic factor (GDNF) to attenuate cochlear damage from intense noise stress. Subjects were exposed to 115 dB SPL one octave band noise centered at 4 kHz for 5 h. They received artificial perilymph with or without GDNF into the left scala tympani at 0.5 microliter/h from 4 days before noise exposure through 8 days following noise exposure. Different concentrations of GDNF (1 ng/ml, 10 ng/ml, 100 ng/ml, and 1 microgram/ml) were applied chronically directly into the guinea pig cochlea via a microcannula and osmotic pump. Noise-induced hearing loss was assessed with pure tone auditory brainstem responses (at 2, 4, 8 and 20 kHz), measured prior to surgery, 1 day before noise exposure, and 7 days following noise exposure. Subjects were killed on day 8 following exposure for histological preparation and quantitative assessment of hair cell (HC) damage. A dose-dependent protective effect of GDNF on both sensory cell preservation and hearing function was found in the treated ears. At 1 ng/ml, GDNF showed no significant protection; at 10 ng/ml, GDNF showed significant HC protection; and at 100ng/ml, it was greater and bilateral. At 1 microgram/ml, GDNF appeared to have a toxic effect under noise stress in some cochleae. These findings indicate that GDNF at certain concentrations can effectively protect the inner ear from noise-induced hearing loss.     

Comparison of normal and impaired hearing. I. Loudness, localization.

Impaired hearing is characterized by high thresholds and reduced loudness. Loudness, however, may quickly recover as it increases rapidly from an elevated threshold. This rapid growth, known as loudness recruitment, is a sign of cochlear impairment and is generally not seen in conductive or retrocochlear impairment. Loudness recruitment means that the hard-of-hearing person detects small changes in intensity near his elevated threshold but he probably does no better than a normal listener at the same SPLs. Recruitment is often accompanied by reduced loudness summation, which means that the loudness of a band of noise does not increase as much with increasing bandwidth as in normal hearing. This reduced summation of loudness is probably why the cochlearly impaired ear has nearly the same threshold for the acoustic reflex to pure tones as to wide-band noise, whereas the normal ear has a much lower threshold to wide-band noise. Corresponding differences between normal and impaired hearing are not found in auditory localization. Rather, the evidence suggests that persons with residual hearing learn to localize sounds reasonably well. Even the inability of many hearing impaired persons to understand a speaker in a noisy environment may result more from a failure of frequency analysis rather than of localization.     

Influence of sympathetic fibers on noise-induced hearing loss in the chinchilla

The influence of the sympathetic efferent fibers on cochlear susceptibility to noise-induced hearing loss is still an open question. In the current study, we explore the effects of unilateral and bilateral Superior Cervical Ganglion (SCG) ablation in the chinchilla on hearing loss from noise exposure, as measured with inferior colliculus (IC) evoked potentials, distortion product otoacoustic emissions (DPOAE), and outer hair cell (OHC) loss. The SCG was isolated at the level of the bifurcation of the carotid artery and removed unilaterally in 15 chinchillas. Another eight chinchillas underwent bilateral ablation. Twelve animals were employed as sham controls. Noise exposure was a 4kHz octave band noise for 1h at 110dB SPL. Results showed improved recovery of DPOAE amplitudes after noise exposure in ears that underwent SCGectomy, as well as lower evoked potential threshold shifts relative to sham controls. Effects of SCGectomy on OHC loss were small. Results of the study suggest that sympathetic fibers do exert some influence on susceptibility to noise, but the influence may not be a major one.     

Interaction of tamoxifen and noise-induced damage to the cochlea

Tamoxifen has been used extensively in the treatment of breast cancer and other neoplasms. In addition to its well-known action on estrogen receptors it is also known to acutely block chloride channels that participate in cell volume regulation. Tamoxifen's role in preventing cochlear outer hair cell (OHC) swelling in vitro suggested that OHC swelling noted following noise exposure could potentially be a therapeutic target for tamoxifen in its role as a chloride channel blocker to help prevent noise-induced hearing loss. To investigate this possibility, the effects of exposure to tamoxifen on physiologic measures of cochlear function in the presence and absence of subsequent noise exposure were studied. Male Mongolian gerbils (2-4 months old) were randomly assigned to different groups. Tamoxifen at ～10 mg/kg was administered to one of the groups. Five hours later they were exposed to a one-third octave band of noise centered at 8 kHz in a sound-isolation chamber for 30 min at 108 dB SPL. Compound action potential (CAP) thresholds and distortion product otoacoustic emission (DPOAE) levels were measured 30-35 days following noise exposure. Tamoxifen administration did not produce any changes in CAP thresholds and DPOAE levels when administered by itself in the absence of noise. Tamoxifen causes a significant increase in CAP thresholds from 8 to 15 kHz following noise exposure compared to CAP thresholds in animals exposed to noise alone. No significant differences were seen in the DPOAE levels in the f(2) = 8-15 kHz frequency range where maximum noise-induced increases in CAP thresholds were seen. Contrary to our original expectation, it is concluded that tamoxifen potentiates the degree of damage to the cochlea resulting from noise exposure.     

A new model for calculating auditory excitation patterns and loudness for cases of cochlear hearing loss

A model for calculating auditory excitation patterns and loudness for steady sounds for normal hearing is extended to deal with cochlear hearing loss. The filters used in the model have a double ROEX-shape, the gain of the narrow active filter being controlled by the output of the broad passive filter. It is assumed that the hearing loss at each audiometric frequency can be partitioned into a loss due to dysfunction of outer hair cells (OHCs) and a loss due to dysfunction of inner hair cells (IHCs). OHC loss is modeled by decreasing the maximum gain of the active filter, which results in increased absolute threshold, reduced compressive nonlinearity and reduced frequency selectivity. IHC loss is modeled by a level-dependent attenuation of excitation level, which results in elevated absolute threshold. The magnitude of OHC loss and IHC loss can be derived from measures of loudness recruitment and the measured absolute threshold, using an iterative procedure. The model accurately fits loudness recruitment data obtained using subjects with unilateral or highly asymmetric cochlear hearing loss who were required to make loudness matches between tones presented alternately to the two ears. With the same parameters, the model predicted loudness matches between narrowband and broadband sound reasonably well, reflecting loudness summation. The model can also predict when a dead region is present.     

Effects of envelope fluctuations on gap detection.

The inherent fluctuations present in narrowbands of noise may limit the ability to detect gaps in the noise; 'dips' in the noise may be confused with the gap to be detected. For subjects with cochlear hearing loss, loudness recruitment may effectively magnify the fluctuations and this could partly account for the reduced ability to detect gaps in noise bands that is usually found in subjects with cochlear hearing loss. In the present experiments we tested these ideas by processing noise bands to alter the amount of envelope fluctuation. The envelopes of the noise bands were raised to a power, N. Powers greater than 1 result in expansion of the envelope (magnified fluctuations, simulating loudness recruitment), while powers less than 1 result in compression of the envelope (decreased fluctuations). Thresholds for detecting gaps in processed noise bands centered at 1 kHz were measured as a function of noise bandwidth and of N. To prevent the detection of spectral changes introduced by the gap or by the processing, stimuli were either presented in background noise, or at a low sensation level (20 dB). Three normally hearing subjects, two subjects with unilateral cochlear hearing loss and two subjects with bilateral cochlear hearing loss were tested. Gap thresholds generally increased with increasing N. This effect was large for small noise bandwidths (50 Hz or less) and smaller for larger noise bandwidths (200 Hz or more). For both the normal and impaired ears, gap thresholds at narrow bandwidths were improved relative to those for unprocessed noise bands (N = 1) by compressing the envelope fluctuations (N < 1). The results support the idea that fluctuations in narrowband noises affect gap detection, and that loudness recruitment may adversely affect the ability to detect gaps in noise bands. They also show that compression of the fluctuations in the noise can improve gap detection.     

Detection of loudness recruitment in patients with retrocochlear lesions using the "Würzburger Hörfeld" loudness scaling

BACKGROUND: The pathogenesis of hearing loss caused by cerebellopontine angle tumors such as acoustic neuromas is unknown. The lack of loudness recruitment is thought to be one of the features of retrocochlear hearing impairment. In contrast to conventional suprathreshold tests, the categorial loudness scaling using the "Würzburger H?rfeld" is a valuable tool to describe the individual perception of sound. The aim of the present study was to analyze the loudness growth rate in patients with acoustic neuroma. PATIENTS AND METHOD: Pure tone and speech audiometry as well as auditory brainstem response and bilateral categorial loudness scaling were performed preoperatively in 54 patients with acoustic neuroma. Loudness scaling was done in free field switching off the contralateral ear by using an ear-plug. RESULTS: An abnormal rapid loudness growth function was found in 38 of the 54 patients (70.4%) at least at one frequency on the tumor side. The contralateral side was effected only in 57.4% of the patients. The incidence of a recruitment depended on the frequency with a maximum at 4 kHz. The slope of the loudness function showed a tendency to increase with increasing hearing loss. CONCLUSIONS: Loudness recruitment is not a rare phenomenon in patients with acoustic neuroma. The underlying cause (a preexisting hair cell damage, hair cell changes resulting from an obstruction of the cochlear blood supply or a disruption of the cochlear efferents) still remains unclear.     

Comparison of functional and morphologic characteristics of mice models of noise-induced hearing loss

Objectives

This study was conducted to compare morphologic and audiologic changes after noise exposure in two different strains of mice (CBA and C57) and to create morphologically proven models of noise-induced hearing loss.

Methods

Mice were exposed to white noise at 110-dB sound-pressure level for 60 minutes at the age of 1 month. Hearing thresholds and outer hair cell functions were evaluated by auditory brainstem response recordings and distortion product otoacoustic emission immediately and 22 days after noise exposure. Cochlear pathology was observed and compared by light and electron microscopic studies.

Results

Both mice strains showed hearing threshold shifts with decreased outer hair cell function immediately and 22 days after noise exposure. More severe auditory brainstem response threshold shifts were observed in C57 mice compared with CBA mice at click, 8-, 16-, and 32-kHz tone-burst stimuli. A cochlear morphologic study demonstrated predominant outer hair cell degeneration at all turns of the cochlea; degeneration was most severe at the basal turn in both mice strains. A scanning electron microscopic study revealed more severe ultrastructural damage of outer hair cells at each turn of the cochlea in C57 mice. The lateral wall of the cochlea was more severely degenerated in CBA mice.

Conclusion

Both mice strains showed consistent, permanent noise-induced hearing loss with different susceptibilities and site vulnerabilities. Further studies to investigate the mechanism of the different degree and cochlear site vulnerability to noise exposure between two mice strains are necessary.     

Consequences of noise- or styrene-induced cochlear damages on glutamate decarboxylase levels in the rat inferior colliculus

Both noise and styrene can injure the cochlea, resulting in a reduction of incoming inputs from the cochlea to the central nervous system. In addition, styrene is known to have neurotoxic properties at high doses. The loss of inputs caused by noise has been shown to be compensated by a new equilibrium between excitatory and inhibitory influences within the inferior colliculus (IC). The main goal of this study was to determine whether styrene-induced hearing loss could also be counterbalanced by a GABAergic adjustment in the IC. For this purpose, rats were exposed to noise (97 dB SPL octave band noise centered at 8 kHz), or to a non-neurotoxic dose of styrene for 4 weeks (700 ppm, 6 h/day, 5 days/week). Auditory sensitivity was tested by evoked potentials, and cochlear damage was assessed by hair cell counts. Glutamate decarboxylase (GAD) was dosed in the IC by indirect competitive enzyme-linked immunosorbent assay. Both noise and styrene caused PTSs that reached 27.0 and 14.6 dB respectively. Outer hair cell (OHC) loss caused by noise did not exceed 9% in the first row, on the other hand OHC loss induced by styrene reached 63% in the third row. Only the noise caused a decrease of GAD of 37% compared to that measured in the controls. No significant modification of GAD concentration has been shown after styrene exposure. Thus, central compensation for cochlear damage may depend on the nature of the ototoxic agent. Unless styrene directly affects IC function, it is reasonable to assume that noise causes a modification of inhibitory neurotransmission within the structure because of impairment of afferent supply to the auditory brainstem. The present findings suggest that central compensation for cochlear damage can preferably occur when afferent fibers are altered.