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.     

Comparative anatomy of melanin pigment in the stria vascularis. Evidence for a distinction between melanocytes and intermediate cells in the cat

Although Corti in 1851 first described the presence of cochlear pigmentation in the stria vascularis (SV) of "very old" cats, modern studies have failed to find pigment consistently in the feline stria. While the variable presence of pigment in the feline SV would appear to contrast with this structure's uniform pigmentation in other mammalian species, variability in both the distribution and abundance of inner ear pigment has rarely been studied in any species. In the present study, the SV was examined light microscopically in sectioned material or whole-mounts from pigmented and albino animals of 5 species, including the cat, guinea pig, rabbit, ferret and mouse. In these species, the SV of each pigmented animal contained varying amounts of melanin pigment and none was found in the albino inner ear. Pigmented guinea pigs contained the most uniformly dense and least variable distribution of strial melanin, followed by the rabbit, mouse, ferret and cat. Several species also displayed more strial pigment apically and less basally. In cats, pigmented cells were principally located adjacent to the strial capillaries. Ultrastructural studies of the stria in pigmented cats revealed that these perivascular cells frequently contained an abundance of pigmented organelles and other structural features which allowed them to be distinguished from intermediate cells.     

Ultrastructural study of the effect of acute hypertension on the stria vascularis and spiral ligament

The effect of acute hypertension, induced in rats by intravenous injection of methoxamine chloride (Mexan), on the stria vascularis and spiral ligament was studied electronmicroscopically with the tracer method of horseradish peroxidase (HRP). Considerable extravasation of HRP occurred in the stria vascularis, due to the increased vesicular transport. The leaked HRP spread into intercellular spaces, but was prevented from spreading towards the endolymph by zonulae occludentes between marginal cells and towards the perilymph by zonulae occludentes between basal cells. The reaction product was occasionally found between basal cells. No leakage of HRP from capillaries was observed in the spiral ligament, although some labelled micropinocytotic vesicles were present in the endothelium. It is suggested that, under acute hypertensive conditions, areas of zonulae occludentes bordering the stria vascularis play an important role as a barrier to HRP, whereas capillaries in the spiral ligament themselves act as a barrier to it.     

庆大霉素对豚鼠血管纹黑色素的影响及其机制

OBJECTIVE: To investigate the effect and its mechanism of gentamicin(GM) on melanin in stria vascularis of guinea pig. METHODS: The differences of auditory thresholds between pigmented and albino guinea pigs, given GM of 150 mg/kg for 7 days, were studied. Moreover, the content of melanosomes, activity of tyrosinase and expression of proliferating cell nuclear antigen(PCNA) in intermediate cells of stria vascularis in gentamicin-treated pigmented guinea pigs were compared with those in control animals by electron microscope and immunohistochemistry, respectively. RESULTS: After gentamicin exposure, the auditory thresholds of all animals increased significantly (P < 0.001), whereas threshold shifts averaged across all frequencies of pigmented animals were much less than those of the albinos(P < 0.001). The number of melanosomes of each examined area (300 microns 2) in intermediate cells was obviously increased from 19.83 +/- 2.74 to 58.33 +/- 16.22. The ratio of tyrosinase reaction products area to the total measured area was significantly increased from 1.65% +/- 0.40% to 3.45% +/- 0.41% after gentamicin exposure. However, the numbers of positive intermediate cells expressing PCNA were 14.08 +/- 2.76 and 13.58 +/- 2.09 before and after gentamicin treatment, respectively. But there was no statistically significant difference between them (P > 0.05). CONCLUSION: The increase of content of melanin in stria vascularis after GM exposure does not result from the change of proliferating activity of melanocytes, but from the enhanced tyrosinase activity. Melanins in stria vascularis may possess the ability to protect the inner ear from ototoxicity of gentamicin.     

Susceptibility of organ of Corti with or without melanin to acoustic overstimulation]

Albino and pigmented guinea pigs were compared in terms of susceptibility to acoustic trauma. The animals were exposed to a 4 kHz pure tone of 120 dB for 60 min. N1 thresholds of CAP were measured before and after the acoustic exposure. Changes in the outer hair cell and stria vascularis were studied using SEM and TEM. After acoustic trauma, N1 thresholds were more elevated in the albino than in the pigmented guinea pigs. Also, pathological changes in the outer hair cell and stria vascularis were more severe in the albino animals. A noteworthy finding in the stria vascularis was that the melanin in intermediate cells had moved into marginal cells. This melanin migration may be possibly involved in mechanisms underlying prevention of acoustic trauma.     

Changes in the capillaries of the stria vascularis after hemorrhagic shock

As a result of severe hemorrhagic shock in guinea pigs, the blood flow in the capillaries of the stria vascularis was blocked, but that of the spiral ligament was unaffected. It is therefore postulated that the thick layer of basal cells and fibrocytes around the stria vascularis and the capillaries leaving the stria vascularis plays an important role in the formation of blood sludging.     

Reduction in the endocochlear potential caused by Cs(+) in the perilymph can be explained by the five-compartment model of the stria vascularis

In an earlier publication (Takeuchi et al., Biophys. J. 79 (2000) 2572-2582), we proposed that K(+) channels in intermediate cells within the stria vascularis may play an essential role in the generation of the endocochlear potential (EP), and we presented an extended version of the five-compartment model of the stria vascularis. In search of further evidence supporting the five-compartment model, we studied the effects of Cs(+) added to the perilymph on guinea pig EP. Cs(+) is known as a competitive K(+) channel blocker. Both the scala tympani and the scala vestibuli of four cochlear turns were perfused at a flow rate of 10 microl/min, and the EP was recorded from the second cochlear turn. Cs(+) at 30 mM caused a biphasic change in the EP; the EP increased transiently from a control level of 89.6 mV to 94.8 mV within 10 min, and then decreased to a steady level of 24.5 mV within the next 40 min. We propose that the initial transient increase in the EP results from Cs(+)-mediated blockade of K(+) conductance in the basolateral membrane of hair cells, and that the subsequent EP decrease is due to effects of Cs(+) on the stria vascularis. We believe that Cs(+) in the perilymph is able to access the stria vascularis by being taken up by fibrocytes in the spiral ligament and then being transported to intermediate cells because it is known that Cs(+) is taken up via Na(+),K(+)-ATPase and that gap junctions connect fibrocytes in the spiral ligament to basal cells and basal cells to intermediate cells. To clarify the effect of intracellular Cs(+) on the electrophysiological properties of intermediate cells, these cells were dissociated from guinea pigs and studied by the whole-cell patch-clamp method. Intracellular Cs(+) depolarized intermediate cells in a dose-dependent manner. In addition, efflux of Cs(+) from the intermediate cell was much less than the efflux of K(+). Thus, Cs(+) may accumulate in the intermediate cell, which depolarizes the cell, which in turn decreases the EP. We conclude that the five-compartment model of the stria vascularis can explain the EP decrease caused by Cs(+) in the perilymph.     

Cochlear findings in the white spotting (Ws) rat

White spotting (Ws) rats possess a c-kit gene mutation at the W locus, resulting in a variety of characteristics including a lack of intermediate cells of the stria vascularis. The present study employs a light microscope (LM), scanning (SEM) and transmission electron microscopes (TEM), diaminobenzidine (DAB) staining techniques and auditory brainstem response (ABR) to investigate the structure and function of the cochlea in 26 homozygous Ws/Ws rats aged 1–6 months. A slight thinning of the stria vascularis and moderate elevation of ABR threshold were about the only defects noted in 1 month animals, while older animals displayed various defects that tended to worsen with age. At 3 months LM revealed pigment granules in the basal turn of most animals, with a loss of pigmentation in the upper turns. The stria vascularis and organ of Corti tended to be well preserved in the lower, pigmented portion, while the upper, unpigmented portion showed severe strial degeneration and some outer hair cell loss. DAB staining revealed a well developed strial capillary net throughout the pigmented portion of the cochlea, with severe degradation in the unpigmented apical portion. ABR thresholds were slightly elevated over 1 month values. At 6 months great differences in degeneration were noted between right and left ears of the same animal.     

Spiral ligament and stria vascularis changes in cochlear otosclerosis: effect on hearing level.

OBJECTIVE: To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization. INTERVENTION: Audiography. MAIN OUTCOME MEASURES: Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques. RESULTS: Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent. CONCLUSION: These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.     

Effects of a single high dose of cisplatin on the melanocytes of the stria vascularis in the guinea pig

The antineoplastic drug cisplatin is known to cause a reduction in endocochlear potential. The hypothesis to be tested was whether a single high dose of cisplatin affects the melanocytes by altering the expression of melanin. Pigmented guinea pigs received a bolus injection of cisplatin (8 mg/kg as a 15-second intravenous infusion). Auditory brainstem response (ABR) thresholds and morphological analysis of the hair cells and the stria vascularis were made 96 h after injection. ABR thresholds were elevated (15-40 dB) at 12-30 kHz and a significant loss of outer hair cells in the more basal regions was found. Cisplatin caused a significantly lower density of melanin in the intermediate cells in the basal region without any signs of apoptosis. Changes in melanin content were not noted in the middle or apical cochlear regions. Significant correlations were found between melanin density, ABR threshold shifts and outer hair cell loss in the region corresponding to 30 kHz. The findings reported here further support the multiple cytotoxic effect of cisplatin on the inner ear.     

胎儿耳蜗血管纹的扫描电镜观察

目的：借助扫描电镜技术观察血管纹的表面结构,以便对血管纹的结构和功能提供新的信息。方法：标本取自尸检3个足月胎儿的6个颢骨,在死后尽可能快速取出耳蜗,经处理后,借助扫描电镜技术观察人胎儿耳蜗血管纹的超微结构。结果：借助扫描电镜技术可从耳蜗基底圈到顶圈,上起前庭膜嵴,下到基底膜的基底嵴全面观察血管纹的各个部分,血管纹边缘细胞表面结构呈圆球形．细胞表面有许多微绒毛。螺旋凸部位有一个细胞移行区,这个区域的边缘细胞表面形态明显不同,细胞细K或呈不规则的多角形细胞,细胞边界微绒毛丰富,显出明显的细胞界限,细胞表面分布均匀的微绒毛。血管纹断面的观察还可获得中间细胞、基底细胞和毛细血管结构。结论：扫描电镜观察胎儿耳蜗血管纹,可获得整个血管纹全貌的表面精细结构,尤其是边缘细胞的表面形态,通过对血管纹断面的观察还可获得中间细胞、基底细胞的精细结构特征,为认识血管纹的结构和功能提供新的信息。     

Proteoglycan arrays in the cochlear basement membrane

Indirect immunofluorescence and transmission electron microscopy were used to investigate the composition and assembly of proteoglycans in the basement membranes of the spiral limbus, basilar membrane, spiral ligament, Reissner's membrane, myelinated nerve fibers, and blood capillaries of the spiral ligament and stria vascularis in the chinchilla cochlea. Four types of basement membrane components: laminin, entactin/nidogen, type IV collagen and heparan sulfate proteoglycans were immunolocalized in all basement membranes in association with heparan sulfate proteoglycans. beta 1 and alpha 1 integrin subunits were also detected along these basement membranes. The concentration of the basement membrane-associated proteins and integrin subunits differed according to the adjacent cell type. Electron microscopy showed that all basement membranes, with exception of those of stria vascularis, consist of two layers: lamina lucida and lamina densa. In the stria vascularis only a homogeneous lamina densa was observed. Cuprolinic blue treatment revealed heterogeneity in the ultrastructure and arrangement of proteoglycans in the cochlear basement membranes. Proteoglycans of the subepithelial basement membrane in the spiral limbus and spiral ligament formed quasi-regular, linear arrays within the lamina lucida, or were located at both sides of the lamina densa in the basilar membrane and Reissner's membrane. In the basement membranes of nerve fibers, and capillaries in the spiral ligament and stria vascularis, proteoglycans were scattered throughout these basement membranes, but showed different concentration and ultrastructural appearance, which may be related to different filtration and mechanical properties. In the basilar membrane, PGs were located above and below the lamina densa. An additional layer of PGs below the lamina densa may function as increased mechanical support of organ of Corti by its interaction with underlying fibrillar collagen layer. In the stria vascularis capillaries, PGs were stained considerably less with Cuprolinic blue and were scattered through the lamina densa of the basement membrane compared to capillaries of spiral ligament. This observation is compatible with a higher permeability of the strial capillaries.     

Freeze fracturing of the human stria vascularis

The stria vascularis is an important functional element in the mammalian cochlea. This special tissue is considered to be the source of the endocochlear potential and thus the driving force for the production of a receptor response to the auditory stimulus. In order to maintain its function, the stria vascularis needs to be separated from the endolymphatic space by a tight seal. This seal is comprised of tight junctions in the marginal cell layer. The junctional arrangement in the stria vascularis is described, utilizing the freeze-fracturing technique which allows the visualization of large expansions of plasma membrane. The marginal cells are generally separated by tight junctions of the moderately tight to tight type. In places, however, even so-called leaky junctions with only a few sealing strands are present. Whereas the intermediate cell layer seems to lack tight junctions, the basal cells are connected by extensive tight junctions more or less covering the entire cell. These junctions seem to form an extremely tight barrier against the spiral ligament. Gap junctions are also present in the tissue. Intermediate cells as well as the basal cells are coupled by gap junctions. In the basal cell layer, gap junctional elements may also be found inside the large tight junctions comprising so-called mixed junctions.     

The development of melanin in the stria vascularis of the gerbil.

One factor that influences noise susceptibility is pigmentation. The aim of this study was to investigate the development of melanocytes, other melanin-containing cells and the amount of melanin in stria vascularis from birth to adult age in the gerbil which has a uniform pigmentation of the fur and eyes, is born without hearing but establishes hearing function at 14-18 days after birth. Changes in the melanin morphology, concentration and distribution have been correlated to the development of the inner ear and to the time period during which hearing function is established, which indicates that the melanocytes in stria vascularis are of importance for the hearing function.     

Distribution of beta-tubulin in guinea pig inner ear

Our previous research had suggested that beta-tubulin might be an autoantigen for autoimmune inner ear disease. In this study, the expression of beta-tubulin in inner ears of normal and tubulin-immunized guinea pigs was examined by immunohistochemical staining. Strong immunoreactivity to beta-tubulin monoclonal antibody was found in stria vascularis, neurons of the spiral ganglion, cochlear nerve fibers and spiral ligament. Diffuse staining was found in the stria vascularis and the neurons of the spiral ganglion, while dense network staining was found in the spiral ligament, the nerve fibers and the vestibular end organs. The semicircular canals, endolymphatic duct and sac were also positively stained. In inner ears of guinea pigs challenged with beta-tubulin, staining intensity was diminished in the stria vascularis, the spiral ligament, and the neurons of the spiral ganglion. The results suggest that beta-tubulin is distributed to most structures of guinea pig inner ear. A challenge to the inner ear by tubulin could change the beta-tubulin distribution and cause degeneration in the spiral ganglion. The results support the hypothesis that beta-tubulin might be an autoantigen for autoimmune inner ear disease.     

Cochlear degeneration in aged rats of four strains.

Animals with various degrees of inbreeding, some of which are albino, are frequently used in biological research. Albinos do not produce melanin and it is therefore absent from the cochlea. While the function of melanin is unknown, it has been hypothesized that it is involved in cochlear homeostasis. It is possible then, that age-related degeneration may be affected by the presence or absence of melanin. We therefore evaluated young (2-6 months old) and aged (24-36 months old) cochleas in 4 different rat strains: albino Fischer 344 and Lewis rats and pigmented Lewis-Brown Norway F1 rats and Brown Norway rats. Cochlear morphology was the same across all strains of young adult animals with the exception that the pigmented animals had small, darkly stained granules in the stria vascularis. The aged pigmented animals all had large granules as well as small ones. Degeneration of spiral ganglion cells in the apical region of the ganglion had occurred in the old animals of all strains. Strial degeneration at the apex was also present in aged animals. There was no correlation between the presence or absence of melanin and the magnitude of cochlear degenerative changes in the aged animals. The presence or absence of melanin therefore, appears to have no effect on cochlear degeneration in the aged rat cochlea.     

正常豚鼠内耳水通道蛋白的表达及意义

目的：检测正常豚鼠内耳组织中水通道蛋白（aquaporins,AQPs）的表达,探讨其在内耳液体平衡中的意义.方法：用免疫组织化学方法,以兔抗大鼠AQP0、1、2、3、5、7、8的多克隆抗体,检测正常豚鼠内耳组织中水通道蛋白亚型0、1、2、3、5、7、8的表达.结果：水通道蛋白亚型0、1、2、3、5、7、8在豚鼠内耳有不同程度、不同模式的表达,其中AQP0仅在血管纹上皮细胞、螺旋神经节细胞有较弱的表达,AQP1的分布见于包绕骨迷路、内淋巴囊、内淋巴管的纤维细胞,基底膜鼓阶面细胞、螺旋韧带纤维细胞、螺旋缘纤维细胞、Corti器、内外螺旋沟、血管纹、椭圆囊壁、球囊壁、螺旋神经节细胞等.AQP2表达在血管纹、Corti器、螺旋神经节细胞和内淋巴囊中.AQP3、7、8的分布类似,在螺旋神经节和包绕膜迷路的组织中均有表达,其中Corti器、内外螺旋沟、血管纹、螺旋神经节表达较强,在螺旋韧带、螺旋缘纤维细胞表达较弱.AQP5则在Corti器、内外螺旋沟、螺旋神经节细胞表达较强,在螺旋韧带纤维细胞表达稍弱.结论：在正常豚鼠内耳中,尤其是膜迷路中有多种水通道蛋白亚型,以不同的方式表达,他们可能在维持膜迷路液体平衡中起着协同作用.     

Importance of type IV collagen, laminin, and heparan sulfate proteoglycan in the regulation of labyrinthine fluid in the rat cochlear duct

The distribution of major components of the basement membrane, such as type IV collagen, laminin, and heparan sulfate proteoglycan (HSPG), was investigated in the rat cochlear duct. Immunofluorescence demonstrated that type IV collagen, laminin and HSPG were distributed along capillaries in the cochlear duct, including the stria vascularis, spiral ligament, spiral prominence and spiral limbus. Additionally, type IV collagen, laminin and HSPG were found to be distributed from the basement membrane of Reissner’s membrane to that of the spiral prominence in a linear pattern. The scala media was surrounded by these basement membrane components, demarcating endolymph from perilymph, along epithelial cells except at the stria vascularis. These findings suggest that type IV collagen, laminin and HSPG create the anatomical separation between endolymph and perilymph, thus indicating that they may be involved in the regulation of fluid transport between the endolymph and perilymph. Received: 3 December 1997 / Accepted: 12 February 1998     

Migration of cochlear lateral wall cells

The role of apoptosis and proliferation in maintenance of cochlear lateral wall cells was examined. The methods employed for detection of apoptosis were the Hoechst fluorescence stain and TUNEL (TdT-mediated dUTP-biotin nick-end-labeling) assay, and proliferations were 5-bromo-2'-deoxyuridine (BrdU) incorporation and presence of the proliferating cell nuclear antigen. The incidence of apoptosis in the strial marginal cell was 50% greater (32.9+/-3.7%) than strial intermediate and basal cells but similar to spiral ligament cells. Although division of marginal strial cells was rarely detected, a significant number of proliferating cells in the remaining stria vascularis and spiral ligament were observed. These data implied that replacement of marginal cells arose elsewhere and could be followed by a BrdU-deoxythymidine pulse-chase study. At 2 h post injection, nuclear BrdU in marginal cells was not detected; however, by 24 h post injection, 20-25% of marginal cell nuclei were BrdU-positive. These observations are consistent with the hypothesis that marginal cells were replaced by underlying cells. Cell migration appears to be an important mechanism for preserving the function and structure of the stria vascularis.     

Effects of Chronic Furosemide Treatment and Age on Cell Division in the Adult Gerbil Inner Ear

Atrophy of the stria vascularis and spiral ligament and an associated decrease in the endocochlear potential (EP) are significant factors in age-related hearing loss (presbyacusis). To model this EP decrease, furosemide was delivered into the round-window niche of young adult gerbils by osmotic pump for seven days, chronically reducing the EP by 30–40 mV. Compound action potential (CAP) thresholds were correspondingly reduced by 30–40 dB SPL at high frequencies. Two weeks after withdrawal of furosemide, the treated ears showed an EP recovery of up to 20–30 mV along with a similar recovery of CAP thresholds. The influence of cell division on furosemide-induced and age-related decline of the EP was examined using a mitotic tracer, bromodeoxyuridine (BrdU). Cell proliferation was examined in three groups: young control, furosemide-treated, and aged cochleas. Sections immunostained for BrdU were bleached with H₂O₂ to eliminate ambiguities with melanin pigment in the inner ear. Cell types positively labeled for BrdU in all three groups included Schwann cells in Rosenthal's canal; glial cells in the osseous spiral lamina; fibrocytes in the limbus, sacculus, and spiral ligament (SL); epithelial cells in Reissner's and round-window membranes; intermediate cells in the stria vascularis; and vascular endothelial cells. Quantitative analysis showed that the mean number of BrdU-positive (BrdU+) intermediate cells in the stria did not differ significantly among the three groups. In contrast, there was a significant increase of BrdU + fibrocytes in the SL of furosemide-treated animals as compared to the young control group. Moreover, there was a significant decrease in labeled fibrocytes in the aged versus the young ears, particularly among the type II and type IV subtypes. The results suggest that the increased fibrocyte turnover in the SL after furosemide treatment may be related to the recovery of EP and CAP thresholds, supporting the hypothesis that fibrocyte proliferation may be essential for maintaining the EP and cochlear function in normal and damaged cochleas. Moreover, the decreased turnover of SL fibrocytes with age may be a contributing factor underlying the lateral wall pathology and consequent EP loss that often accompanies presbyacusis.