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PubMed1981

Changes in cation contents of stria vascularis with ouabain and potassium-free perfusion.

Perfusion of the perilymphatic space of guinea pig cochleae with K-free medium leads to a gradual decline of the endocochlear potential (EP) over 30-50 min to a negative value (mean: -12 mV). The input resistance of scala media does not decrease during this time. The ATP and K content of the stria vascularis are reduced by similar amounts (26 and 34%, respectively) during this period. Perfusion of 1 mM ouabain produces a different pattern of response: strial ATP remains normal while strial K content is strongly reduced (by 77%). Strial Na rises in a complementary way to the K loss. These results demonstrate that a reduction of the K concentration of the perilymph leads to an inhibition of the generator of the positive component of the EP rather than to a general increase of cochlear duct membrane conductance. In addition, they suggest, in concert with other considerations (such as the slower rate of decline of the EP during K-free vascular perfusion (Wada, J., Kambayashi, J., Marcus, D.C. and Thalmann, R (1979): Arch. Otorhinolaryngol. 225, 79-81)), that the mode of action may be different from that of ouabain. In spite of the lack of teleological support, we offer the hypothesis that the strial generator of the EP may primarily utilize K from perilymph and that vascular K may not have access to the generator.

Adenosine Triphosphate↗
PubMed1998

The significance of endothelin for generation of endocochlear potential.

The role of intermediate cells (ICs) in the stria vascularis (SV) of the cochlear ducts in the generation of endocochlear potential (EP) is clear because certain mutants cannot generate EP. Recent reports have shown that endothelin (ET) stimulates or inhibits the function of Na+, K(+)-ATPase in various organs. This study was designed to examine the immunocytochemical localization of ET and its receptor in the SV. The cochlear ducts of WBB6F1 (+/+) mice and mutants (W/Wv) devoid of the ICs were used for light and electron microscopic immunocytochemistry using rabbit anti-ET-1, ET-3, and ETA receptor antisera. The location of Na+, K(+)-ATPase using rabbit anti-rat Na+, K(+)-ATPase was also examined. Immunoreactivity to Na+, K(+)-ATPase was seen in the marginal cells (MCs) in both species. Immunoreactivity to ET-1 and ET-3 was preferentially localized in the rough endoplasmic reticulum and cytoplasmic vesicles of the ICs and along the plasma membrane of the ICs and in the MCs apposed to the ICs. Immunoreactive sites for ETA were almost identical to those of ET-1 and ET-3. Because Na+, K(+)-ATPase activities also exist in the MCs of the mutants, it appears likely that ET, synthesized and released by the ICs, may participate in generation of EP by regulating the function of Na+, K(+)-ATPase for production of the endolymph of the MCs.

Animals↗
PubMed1992

Lateral wall Na,K-ATPase and endocochlear potentials decline with age in quiet-reared gerbils.

Changes in the integrity of cochlear ion transport systems with age were examined in gerbils raised for 5-38 months in a quiet environment. Ion transport function was assessed by light microscopic immunohistochemical staining for the enzyme, Na,K-ATPase and by measurement of the endocochlear potential (EP). Small foci of strial atrophy accompanied by loss of immunostaining for Na,K-ATPase were observed in the stria vascularis of the apical and basal turns as early as 5 months of age. Cochleas from 29-38 month-old gerbils showed a loss of immunostaining for Na,K-ATPase in the stria in most of the apical turn with the degeneration extending well into the middle turn in many of the oldest ears. The extent of strial atrophy and loss of immunoreactive Na,K-ATPase in the basal turn varied considerably among the oldest cochleas. Populations of lateral wall fibrocytes (type II fibrocytes) normally rich in Na,K-ATPase exhibited a corresponding decrease in enzyme content in regions of advanced strial atrophy. The volume of immunostained stria vascularis correlated well with the magnitude of the resting EP. The results demonstrate that lateral wall ion transport systems in the gerbil cochlea degenerate as a function of age. The findings also provide good evidence for a functional relationship between the stria vascularis and the Na,K-ATPase-rich type II fibrocytes in generating and maintaining the EP.

Animals↗
PubMed1993

Differential physiologic effects of perfusion of scala tympani versus scala vestibuli in the ischemic cochlea.

The effectiveness of perilymphatic perfusion with oxygenated artificial media upon the endocochlear potential (EP) was measured during systemic ischemia in the guinea pig. Differences in the effects of perfusion of the two perilymphatic scalae were determined. Perfusion of scala vestibuli with oxygenated artificial perilymph at a high flow rate resulted in complete recovery of the EP to the pre-ischemic level, whereas perfusion of scala tympani with the same medium was unable to effect complete recovery. The recovery obtained by perfusion of scala tympani was about half that obtained of scala vestibuli. The pO2 in scala media was measured during perfusion by means of oxygen-sensitive microelectrodes. perfusion of scala vestibuli led to an approximately two-fold higher pO2 in scala media than perfusion of scala tympani. During perfusion, the pO2 in scala media varied dependent upon depth of electrode insertion, with a gradient decreasing toward the stria vascularis, a direction opposite to that seen under normal metabolic conditions. These findings suggest that, in the ischemic cochlea, oxygen enters scala media more easily from scala vestibuli across Reissner's membrane than from scala tympani via the basilar membrane/organ of Corti complex.

Animals↗
PubMed1999

[Differences in furosemide-induced changes of summating potential and endocochlear potential in guinea pigs].

OBJECTIVE: To investigate the physiological properties of summating potential (SP) and to compare the different changes between SP and endocochlear potential (EP) induced by Furosemide in guinea pigs. METHODS: SP in response to clicks with alternative polarities at 105 dB peSPL was recorded from a electrode in the facial nerve canal. EP was measured with a glass microelectrode in the basal turn of the cochlea. SP and EP were observed simultaneously and continuously after injection of Furosemide or the solution of Furosemide-bovine serum albumin injected into the jugular vein of the animal. RESULTS: Before furosemide application, only SP could be recorded with small or without +SP. After furosemide injection, EP declined dramatically followed by reduction of the -SP which quickly vanished, while +SP appeared or the amplitude increased. When EP recovered to a certain level, +SP disappeared or dramatically decreased and then -SP reappeared. The amplitude of -SP increased progressively with EP recovery. Both -SP and EP recovered to the pre-injected level in 60 min after the furosemide application. CONCLUSION: The results suggest that Furosemide induced distinct changes of -SP and +SP, the two components of SP. The changes of -SP amplitude was consistent with that of the EP value, while the changes of +SP amplitude were contrary to that of the EP value.

Animals↗
PubMed1992

Characteristics of stria vascularis melanocytes of viable dominant spotting (Wv/Wv) mouse mutants.

The Wv mutation lies in the kinase domain of the proto-oncogene c-kit which is expressed in a variety of cells including neural crest derived melanoblasts. The mutation results in the abnormal migration, proliferation, survival and/or differentiation of melanoblasts. Viable Dominant Spotting (Wv/Wv) mouse mutants have a white coat due to the absence of melanocytes. The majority of these animals have no melanocytes within the stria vascularis and no endocochlear potential (EP). A proportion of homozygous mutants partially escape the effects of the mutation: 47.2% of pinnae and 21% of vestibular regions were pigmented and 10.8% of ears had an EP. All ears with an EP that were available for histology had some pigmentation of the stria. There was no obvious correlation between external and internal spotting in Wv/Wv mice, and asymmetrical pigmentation of the ears was common. Both light and dark intermediate cells (which are derived from melanocytes) were present in the middle and/or basal turns of these cochlear ducts and they appeared to function normally in enabling the stria to produce an EP (although the EP was usually lower than normal). This suggests that the c-kit gene product is needed only during development of the stria, and not for mature melanocyte function because the melanocytes present in the mutant strias were carrying the mutant version of the c-kit gene. Melanocytes were similar in appearance in controls and mutants, except that fewer melanin granules were observed in the strias of Wv/Wv mice. The observations that strial melanocytes with very few melanin granules in Wv/Wv mutants are able to support EP production, together with previous observations that albino animals with strial melanocytes but no melanin have a normal EP, suggest that melanocytes but not melanin are essential for normal strial function.

Animals↗
PubMed1998

Laser scanning confocal microscopy of the hearing organ: fluorochrome-dependent cellular damage is seen after overexposure.

In order to combine laser confocal microscopy with physiological measurements, a number of conditions have to be met: the dye must not be toxic to the cells the laser light itself must not damage the cells; and the excitation of the fluorochrome during imaging must not generate products with toxic effects. We have investigated these conditions the hearing organ of the guinea pig. Two dyes were used, namely, calcein-AM, which is metabolized in vital cells to a fluorescent product in the cytoplasm, and a lipophilic membrane dye. The effect of the dyes on cell function was tested in the intact hearing organ, maintained in the isolated temporal bone, by measuring the electrophysiological potentials generated by the sensory cells in response to tone pulses. The loading of the cells with the dyes had no adverse effects. The effect of the laser beam was explored on isolated coils from the cochlea. In two preparations, the specimens viewed in the confocal system were fixed and processed for electron microscopy. Identified cells were followed before, during, and after laser exposure and could ultimately be examined at the ultrastructural level. Exposure to the laser beam did not cause damage in unstained cells, even at high intensities. In stained tissue, confocal microscopy could safely be performed at normal beam intensity without causing ultrastructural changes. At high intensities, about 100 times normal for 60 times as long, irradiation damage was seen that was selective in that the cells stained with the different dyes exhibited damage at the different sites corresponding to the subcellular location of the dyes. Cells stained with calcein showed lysis of mitochondria and loss of cytoplasmic matrix, whereas cells stained with the styryl membrane dye showed swelling of subsurface cisternae, contortion of the cell wall, and shrinkage. The styryl dyes, in particular, which selectively stain the sensory and neuronal cells in the organ of Corti, could be exploited for phototoxic use.

Animals↗
PubMedDate not supplied

Cochlear summating potential to broadband clicks detected from the human external auditory meatus. A study of subjects with normal hearing for age.

The cochlear summating potential (SP) preceding the auditory nerve compound action potential (AP) was elicited by broadband alternating condensation and rarefaction clicks and recorded by noninvasive electrodes from the external auditory meatus (EAM) of 60 volunteers of both sexes, 12 to 67 years old, who had normal hearing for age. Quantitative data were obtained on: the number of ears displaying measurable SPs; the SP detection level; the SP onset, peak and rise times; the duration of the SP-AP complex; the SP amplitude; and the SP/AP amplitude ratio. Previously unknown relationships were unveiled between the amplitude, but not the temporal, measures of the SP and laterality, sex, age, and audiometrically determined hearing thresholds to 4 to 8 kHz tones. The highest correlations were obtained with these last thresholds, which suggested that receptors in the basal turn of the cochlea played a dominant role in the generation of the EAM-detected SP. To improve on existing techniques for determining abnormal SP elevation, a multiple regression method was devised that utilized sex, age, 4 to 8 kHz hearing thresholds, and AP voltage to establish upper normal limits of SP amplitude for individual subjects and ears.

Acoustic Stimulation↗
PubMed1998

CD1 hearing-impaired mice. I: Distortion product otoacoustic emission levels, cochlear function and morphology.

The levels of distortion product otoacoustic emissions (DPOAEs) were measured in a strain of hearing-impaired mutant mice (CD1) at various stages of outer hair cell impairment and compared to those of a control inbred strain (CBA/J). Parallel measurements of cochlear potentials and auditory brainstem evoked responses (ABRs) were performed and surface preparations of organs of Corti were observed using phalloidin staining of filamentous actin. Comparison of DPOAEs (elicited by stimulus levels of 60 and 70 dB SPL) with standard functional tests allowed the categorization of CD1 ears into two groups on the basis of the presence or absence of DPOAE, which corresponded to mean ABR thresholds greater or less than 40 dB nHL respectively. When adopting ABR threshold as the gold standard, this procedure yielded rates of false-positives and -negatives ranging from 5 to 16%. However, individual predictions of electrophysiological function from DPOAE levels were not accurate, owing to their large variance, and attempts to optimize stimulus levels did not reduce this variance. In contrast, the profiles of DPOAE level vs. f2 exhibited large correlations with ABR threshold profiles as a function of f2. It was also noteworthy that the mean levels of DPOAEs in CD1 mice recorded in frequency intervals with normal ABR thresholds were significantly smaller than those of CBA/J mice. Although hearing loss was revealed early both by DPOAEs and by other functional tests, surface preparations often remained normal until about 3-4 months of age.

Acoustic Stimulation↗
PubMed1991

[Evoked oto-acoustic emissions (EOE) as screening method in infants].

The authors consider the problems of the early diagnosis of paediatric hypoacusis, presenting a study done on twenty audiological high risk children that were subjected to audiometric screening by delayed cochlear otoacoustic emissions (EOE) and brainstem auditory evoked potentials (BEAPs). Eighteen of twenty children that were examined were normal, while two had bilateral sensorineural hearing loss. EOE were evoked in all patients that presented normal BAEP thresholds, while they were absent in deaf subjects. Evoked otoacoustic emissions research allows us to identify two groups of subjects: those with normal EOE who can be considered normal hearing subjects, and those without EOE who may present a disturbed auditory system. Nevertheless, EOE testing does not allow us to judge the type of hearing loss. The time for EOE testing is approximately five minutes for each subject. On the grounds of their experience, the authors conclude that EOE testing represents a useful and reliable test which differentiates normal auditory function subjects from hypoacoustic ones. Compared to other techniques used in audiological paediatric diagnosis, such as reactometry, BOEL test and Crib. O. Gram, which present the possibility of false positive and false negative results, and BSERA, which even if reliable, must be limited to few selected audiological high-risk subjects, EOE is easy to implement and readily available. Major limitations of this technique seem to be the possibility of false positives, and the impossibility to specify localisation and type of the hearing loss by EOE only.

Cochlear Microphonic Potentials↗
PubMed1984

Auditory evoked potentials--the cochlear summating potential in detection of endolymphatic hydrops.

With an expanded clinical and normative SP amplitude series, we have re-examined the incidence of SP enlargement in clinically defined Meniere and cochlear ears. The overall incidence of SP enlargement in the expanded series is somewhat less than that found in our previous study (56% versus 68%). This difference may be due to considerable preselection of patients included in the previous smaller clinical population, since many of these patients were recruited for the study because of diagnosed Meniere's disease. In contrast, the present, larger clinical population was selected from our normal service referral base, and thus contains a much higher percentage of diagnostic problems. The comparison between SP enlargement and hearing levels demonstrates that the SP test for Meniere's disease must be interpreted in the light of high-frequency hearing levels. If the patient has normal or near-normal hearing (4- to 8-kHz hearing levels 25 dB or less), SP enlargement will not be a good criterion for detecting the presence of Meniere's disease. Gibson and colleagues and Kumagami and associates have reported similar observations. Also, in the presence of severe high-frequency hearing loss (above about 70 dB), SP enlargement occurs relatively infrequently among ears with clinical diagnoses of Meniere's disease. However, in the mid-range (25 to 70 dB) of high-frequency loss, SP enlargement appears to provide a reasonably accurate test for Meniere's disease (with a "hit rate" among clinically defined Meniere ears of about 71%).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Stem↗
PubMed2006

Gastric type H+,K+-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential.

Cochlear endolymph has a highly positive potential of approximately +80 mV known as the endocochlear potential (EP). The EP is essential for hearing and is maintained by K(+) circulation from perilymph to endolymph through the cochlear lateral wall. Various K(+) transport apparatuses such as the Na(+),K(+)-ATPase, the Na(+)-K(+)-2Cl(-) cotransporter, and the K(+) channels Kir4.1 and KCNQ1/KCNE1 are expressed in the lateral wall and are known to play indispensable roles in cochlear K(+) circulation. The gastric type of the H(+),K(+)-ATPase was also shown to be expressed in the cochlear lateral wall (Lecain E, Robert JC, Thomas A, and Tran Ba Huy P. Hear Res 149: 147-154, 2000), but its functional role has not been well studied. In this study we examined the precise localization of H(+),K(+)-ATPase in the cochlea and its involvement in formation of EP. RT-PCR analysis showed that the cochlea expressed mRNAs of gastric alpha(1)-, but not colonic alpha(2)-, and beta-subunits of H(+),K(+)-ATPase. Immunolabeling of an antibody specific to the alpha(1) subunit was detected in type II, IV, and V fibrocytes distributed in the spiral ligament of the lateral wall and in the spiral limbus. Strong immunoreactivity was also found in the stria vascularis. Immunoelectron microscopic examination exhibited that the H(+),K(+)-ATPase was localized exclusively at the basolateral site of strial marginal cells. Application of Sch-28080, a specific inhibitor of gastric H(+),K(+)-ATPase, to the spiral ligament as well as to the stria vascularis caused prominent reduction of EP. These results may imply that the H(+),K(+)-ATPase in the cochlear lateral wall is crucial for K(+) circulation and thus plays a critical role in generation of EP.

Animals↗
PubMed1990

Long term effects of intense sound on endocochlear DC potential.

Changes in endocochlear DC potential (EP) after single and repeated intense sound exposure and negative EP induced by anoxia were observed in guinea pigs with passage of time. The intense sound used was a pure tone of 2 kHz at 145 dB SPL for 4 h. The single exposure group was divided into 8 groups of 1, 2, 5, 10, 20, 30, 45, and 60 days after sound exposure. The EP level dropped remarkably in the 1 and 2 day groups and recovered almost completely in the remaining groups. In the 60 day group, EP was significantly higher than that of the control group. The double exposure group consisted of 1, 2, 5, 10, 20, and 30 day groups after the second exposure at an interval of 30 to 40 days. EP in the 1, 2, 5, and 10 day groups was significantly lower than the control level and in the 20 and 30 day groups was almost the same as that of the controls. In all groups after single and double sound exposure, disappearance of negative EP during anoxia was observed. The EP decrease after sound exposure was apparently caused by a mechanical but reversible lesion at the stria vascularis. The disappearance of negative EP after sound exposure was thought to be induced by an irreversible lesion of Corti's organ.

Animals↗
PubMed2004

Compartmentalization established by claudin-11-based tight junctions in stria vascularis is required for hearing through generation of endocochlear potential.

Claudins are cell adhesion molecules working at tight junctions (TJs) that are directly involved in compartmentalization in multicellular organisms. The cochlea includes a rather peculiar compartment filled with endolymph. This compartment is characterized by high K+ concentration (approximately 150 mM) and a positive endocochlear potential (approximately 90 mV; EP), both indispensable conditions for cochlear hair cells to transduce acoustic stimuli to electrical signals. These conditions are thought to be generated by the stria vascularis, which is adjacent to the endolymph compartment. The stria vascularis itself constitutes an isolated compartment delineated by two epithelial barriers, marginal and basal cell layers. Because TJs of basal cells are primarily composed of claudin-11, claudin-11-deficient (Cld11-/-) mice were generated with an expectation that the compartmentalization in stria vascularis in these mice would be affected. Auditory brainstem response measurements revealed that Cld11-/- mice suffered from deafness; although no obvious gross morphological malformations were detected in Cld11-/- cochlea, freeze-fracture replica electron microscopy showed that TJs disappeared from basal cells of the stria vascularis. In good agreement with this, tracer experiments showed that the basal cell barrier was destroyed without affecting the marginal cell barrier. Importantly, in the endolymph compartment of Cld11-/- cochlea, the K+ concentration was maintained around the normal level (approximately 150 mM), whereas the EP was suppressed down to approximately 30 mV. These findings indicated that the establishment of the stria vascularis compartment, especially the basal cell barrier, is indispensable for hearing ability through the generation/maintenance of EP but not of a high K+ concentration in the endolymph.

Alleles↗
PubMed1998

Intercellular junctional maturation in the stria vascularis: possible association with onset and rise of endocochlear potential.

The postnatal maturation of intercellular junctions of marginal and basal cells of the stria vascularis was examined in the gerbil using thin sections and freeze fracture techniques. Immunohistochemical methods were used to determine the presence of Na,K-ATPase postnatally. The onset and growth of endocochlear potential (EP) was also measured. In marginal cells, the apical surface and junctional region around the apical pole of the cell was found to have adult-like characteristics by the time of onset of EP, whilst the increase in staining for Na.K-ATPase temporally coincided with an increasing density of intra-membrane protein particles on the infoldings of marginal cell lateral membranes. Maturation of the junctional specialisations of the basal cells was found to correspond temporally with the period of onset and rise of EP. Tight junctions between basal cells first appeared as small, broken strands composed of widely spaced particles at 6 days after birth (DAB). These junctional strands increased in number and in particle density until adult-like at 16 DAB when they covered large areas of the basal cell lateral membrane. Gap junctions on the apical membrane of basal cells first appeared as small patches of loosely packed junctional elements at 6 DAB. Between 8 and 16 DAB the area of membrane occupied by the gap junctions increased, reaching a mature conformation by 18 DAB. The results suggest that EP maturation is dependent upon the development of sealing between the basal cells by tight junctions and also the establishment and development of gap junctions in the apical plasma membrane of basal cells, associated with intermediate cells.

Age Factors↗
PubMed1992

Dependence of endocochlear potential on basolateral Na+ and Cl- concentration: a study using vascular and perilymph perfusion.

Inside-positive endocochlear potential (EP) and high potassium concentration in the endocochlear duct are generated by transepithelial K+ transport in marginal cells of the stria vascularis. In order to estimate the degree of involvement of Na+ and Cl- in K+ transport in marginal cells, EP in guinea pigs was measured under artificial vascular and perilymphatic perfusion in situ. Na+ depletion due to both vascular and perilymphatic perfusion decreased EP by -10.0 +/- 4.1 mV (delta EP = -86 +/- 5.2 mV, n = 5) from the control value of 78 +/- 4.3 mV (p < 0.01). Cl- depletion due to vascular and perilymphatic perfusion also decreased EP by -10.0 +/- 4.9 mV (delta EP = 8.5 +/- 4.8 mV, n = 6) from the control value of 77 +/- 5.1 mV (p < 0.01). However, under either vascular or perilymphatic perfusion, even lowering of Na+ or Cl- concentration in the perfusate decreased EP only slightly compared to the results under both vascular and perilymphatic perfusion. Furosemide, a blocker of Na+/K+/2Cl- symport, decreased EP under vascular perfusion. This dependency of EP on basolateral Na+ and Cl- concentration strongly suggests that K+ transport by the marginal cell is dependent on the basolateral Na+ and Cl- concentration, and that Na+/K+/2Cl- symport is raised as a possible mechanism for Na+ and Cl- dependency of EP.

Animals↗
PubMed1992

Effects of anoxia on the cochlear summating potential in the guinea pig.

The cochlear summating potential (SP) was recorded extracochlearly from the apex and the round window in 25 guinea pigs, applying anoxia during periods of 1-2 min. For 2 and 8 kHz tone pips at 80 and 60 dB SPL, respectively, the initially negative SP at the apex diminished and even became positive during oxygen cut-off. After restoration of oxygenation, the change in SP reversed direction and was followed by a large negative undershoot. At the round window, the initially positive SP evoked by 8 kHz, 60 dB SPL tone pips followed exactly the same time course, but with inverted polarity, while the majority of the recordings of the initially negative SP evoked by 2 kHz, 80 dB SPL tone pips followed a course similar to the apical negative SP. However, the negative round window SP showed only slight polarity reversal and no undershoot. A small number of the recordings at the round window for 2 kHz showed an increase of the negative SP during anoxia followed by a decline of the SP and recovery after anoxia. The similar time course of the initially negative SP at the apex and the initially positive SP at the round window failed to support the hypothesis of a multi-component SP. However, the polarity reversal during anoxia and the different reactions to anoxia of the 2 kHz round-window SP suggest that the SP may consist of several different components.

Animals↗
PubMed2003

Age-related changes in cochlear endolymphatic potassium and potential in CD-1 and CBA/CaJ mice.

The CD-1 mouse strain is known to have early onset of hearing loss that is progressive with aging. We sought to determine whether a disturbance of K+ homeostasis and pathological changes in the cochlear lateral wall were involved in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain which has minimal AHL. In the present study, the endocochlear potential (EP) and endolymphatic K+ concentration ([K+]e) were measured in both strains of mice with double-barrel microelectrodes at "young" (1-2 mo) and "old" (5-9 mo) ages. CBA/CaJ mice displayed no changes with aging in EP and [K+]e of the basal turn. In the apical turn, there was a small positive shift of the EP (10 mV) with aging under both normoxic and acute anoxic conditions (-EP), without any change of [K+]e. Further, there were no obvious pathological changes in the lateral wall of CBA/CaJ mice. By contrast, old CD-1 mice displayed a significantly reduced [K+]e by 30% in both basal and apical turns with no significant changes in normoxic EP. The -EP in the apical turn was significantly reduced in magnitude by 6 mV. A severe loss of cells with aging was observed in the region of type IV fibrocytes of the apical and basal turns and of type II fibrocytes in the basal turn. A complete degeneration of organ of Corti was also observed at the basal turn of old CD-1 mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-1 mice were similar to those of an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a primary etiology of AHL of CD-1 mice. These findings have ramifications for our understanding of AHL and for interpretation of genetic mutations in a CD-1 background.

Aging↗