Decrease In Endocochlear Potential Research Articles

Cytokines and Inflammation in Meniere Disease.

Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evidence to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.

Suppression of Connexin 43 Leads to Strial Vascular Hyper-Permeability, Decrease in Endocochlear Potential, and Mild Hearing Loss.

Objective: Connexin 43 (Cx43) is a protein constituent of gap junctions (GJs) in various barrier cells, especially astrocytes and microglia of the blood-brain-barrier (BBB), where it plays an important role in intercellular communication and regulation of the barrier. Despite the importance of Cx43 in other blood barriers, not much attention has been paid to expression and function of Cx43 in the blood-labyrinth-barrier (BLB) of the stria vascularis in the cochlea.Methods: We used multiple research approaches, including immunocytochemical staining, patch-clamp dye loading technique, real-time quantitative reverse transcription (RT)-PCR, western blot, measurement of endocochlear potential (EP) with an electrode through the scala media, and auditory brainstem response to test hearing function.Results: We found Cx43 expressed in vascular endothelial cells (ECs) and perivascular resident macrophages (PVMs) in the stria vascularis of adult C57BL/6 mouse cochleae. In particular, we found Cx43 expressed in foot processes of PVMs at points of contact with the endothelium. Consistent with Cx43 expression in vivo, we also found Cx43 expressed in EC-EC and EC-PVM interfaces in a co-cultured cell line model. Using a patch-clamp dye loading technique, we demonstrated that Alexa Fluor® 568 dye injected into PVMs diffuses to connected neighboring ECs. The functional coupling between the ECs and PVMs is blocked by 18α-Glycyrrhetinic acid (18α-GA), a GJ blocker. Suppression of Cx43 with small interfering RNA (siRNA) in vivo significantly elevated hearing threshold and caused the EP to drop and the blood barrier to become more permeable. In further study, using in vitro primary EC cell line models, we demonstrated that suppression of Cx43 disrupts intercellular tight junctions (TJs) in the EC monolayer and increases endothelial monolayer permeability.Conculsion: Taken together, these findings underscore the importance of Cx43 expression in the normal ear for maintaining BLB integrity, normal EP, and hearing function.

KCNK5 channels mostly expressed in cochlear outer sulcus cells are indispensable for hearing.

In the cochlea, K+ is essential for mechano-electrical transduction. Here, we explore cochlear structure and function in mice lacking K+ channels of the two-pore domain family. A profound deafness associated with a decrease in endocochlear potential is found in adult Kcnk5−/− mice. Hearing occurs around postnatal day 19 (P19), and completely disappears 2 days later. At P19, Kcnk5−/− mice have a normal endolymphatic [K+] but a partly lowered endocochlear potential. Using Lac-Z as a gene reporter, KCNK5 is mainly found in outer sulcus Claudius', Boettcher's and root cells. Low levels of expression are also seen in the spiral ganglion, Reissner's membrane and stria vascularis. Essential channels (KCNJ10 and KCNQ1) contributing to K+ secretion in stria vascularis have normal expression in Kcnk5−/− mice. Thus, KCNK5 channels are indispensable for the maintenance of hearing. Among several plausible mechanisms, we emphasize their role in K+ recycling along the outer sulcus lateral route.

Effects of perilymphatic pressure, sodium nitroprusside, and bupivacaine on cochlear fluid pH of guinea pigs

Conclusions: Hydrostatic positive pressure and vasoconstrictor acidified the cochlear fluids, whereas the vasodilator made the fluids alkaline. CBF might play a role in regulating cochlea fluid pH. Objectives: Cochlea fluid pH is highly dependent on the HCO3−/CO2 buffer system. Cochlear blood flow (CBF) supplies O2 and removes CO2. It is speculated that cochlear blood flow changes might affect the balance of the HCO3−/CO2 buffer system in the cochlea. It is known that the elevation of inner ear pressure decreases the CBF, and local application of vasodilating or vasoconstricting agents directly to the cochlea changes the CBF. The purpose of this study was to elucidate the effect of positive hydrostatic inner ear pressure and application of a vasodilator and vasoconstrictor of cochlear vessels on the pH of the endolymph and perilymph. Methods: The authors performed animal physiological experiments on 30 guinea pigs. Hydrostatic positive pressure was infused through a glass capillary tube inserted into the scala tympani of the basal turn. The vasodilator, nitric oxide donor (sodium nitroprusside; SNP), and the vasoconstrictor, bupivacaine, were placed topically onto the round window of the guinea pig cochlea. Endolymph pH (pHe) and endocochlear potential (EP) were monitored by double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea. During the topical application study, scala vestibuli perilymph pH (pHv) was also measured simultaneously in the second turn. Results: The application of hydrostatic positive pressure caused a decrease in pHe and EP. Positive perilymphatic pressure caused the endolymph to become acidic pressure-dependently. Application of 3.0% SNP evoked an increase in both the pHe and pHv, following by a gradual recovery to baseline levels. On the other hand, 0.5% bupivacaine caused a decrease in both the pHe and pHv. The EP during topical application showed slight, non-significant changes.

Change in Endocochlear Potential During Experimental Insertion of a Simulated Cochlear Implant Electrode in the Guinea Pig

Preservation of residual hearing during cochlear implantation is important. This study investigated changes in endocochlear potential (EP) during simulated cochlear implant (CI) electrode insertion. Laboratory animal study. Academic hospital laboratory. Guinea pigs were divided into 4 groups: cochleostomy only (4 animals), suction after cochleostomy (5 animals), simulated CI electrode insertion parallel to the longitudinal axis of the scala tympani without suctioning (7 animals), and simulated CI electrode insertion toward the modiolus without suctioning (7 animals). The EP was measured from the second turn of the cochlea, and the values after 20 minutes were compared. The EP showed little change at 20 minutes after cochleostomy with a nearly normal value of 84.83 ± 2.12 mV. Suctioning of the perilymph from the cochleostomy site caused a slight acute reduction in EP by about 6 mV, and the value at 20 minutes after cochleostomy was 78.64 ± 4.42 mV. Insertion of the simulated CI electrode parallel to the longitudinal axis of the scala tympani caused a slight decrease in EP to 78.91 ± 5.06 mV. Insertion toward the modiolus caused a marked decrease in EP to 54.13 ± 4.42 mV at 20 minutes after the treatment, significantly lower compared with the other 3 groups. EP was well preserved during carefully performed surgical procedures of simulated CI electrode insertion, but it decreased significantly if the simulated CI electrode was inserted toward the modiolus. Careful attention is necessary to ensure the correct direction of CI electrode insertion to preserve residual hearing. Use of suction should be minimized if possible.

Ca2+ regulation of endocochlear potential in marginal cells

We examined the effect of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) in marginal cells on the asphyxia- or furosemide-induced decrease in the endocochlear potential (EP) by perfusing the endolymph with or without a Ca(2+) chelator or inhibitors of Ca(2+)-permeable channels or Ca(2+)-pump during transient asphyxia or intravenous administration of furosemide. We obtained the following results. (1) Endolymphatic administration of SKF96365 (an inhibitor of TRPC and L-type Ca(2+) channels) or EGTA-acetoxymethyl ester (EGTA-AM) significantly inhibited both the transient asphyxia-induced decrease in EP (TAID) and the furosemide-induced decrease in EP (FUID). (2) Endolymphatic perfusion with nifedipine significantly inhibited the TAID but not the FUID. (3) The recovery from the FUID was significantly suppressed by perfusing the endolymph with EGTA-AM, nifedipine, or SKF96365. (4) Endolymphatic administration of thapsigargin inhibited both the FUID and TAID. (5) The recovery rate from the FUID was much slower than that from the TAID, indicating that furosemide may inhibit the Ca(2+)-pump. (6) A strong reaction in immunohistochemical staining for TRPC channels was observed in the luminal and basolateral membranes of marginal cells. (7) A positive staining reaction for the gamma subunit of epithelial Na(+) channels was observed in the luminal and basolateral membranes of marginal cells. (8) Positive EP was diminished toward 0 mV by the endolymphatic perfusion with 10 muM amiloride or 10 muM phenamil. Taken together, these findings suggest that [Ca(2+)](c) regulated by endoplasmic Ca(2+)-pump and Ca(2+)-permeable channels in marginal cells may regulate the positive EP, which is partly produced by the diffusion potential of Na(+) across the basolateral membrane in marginal cells.

Endocochlear potential depends on Cl− channels: mechanism underlying deafness in Bartter syndrome IV

Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a beta-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K(+)-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd(-/-) mice thus demonstrate a novel function of Cl(-) channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV.

Effects of CO2/HCO3− in Perilymph on the Endocochlear Potential in Guinea Pigs

The effect of CO(2)/HCO(3)(-) on the endocochlear potential (EP) was examined by using both ion-selective and conventional microelectrodes and the endolymphatic or perilymphatic perfusion technique. The main findings were as follows: (i) A decrease in the EP from approximately +75 to approximately +35 mV was produced by perilymphatic perfusion with CO(2)/HCO(3)(-)-free solution, which decrease was accompanied by an increase in the endolymphatic pH (DeltapH(e), approximately 0.4). (ii) Perilymphatic perfusion with a solution containing 20 mM NH(4)Cl produced a decrease in the EP (DeltaEP, approximately 20 mV) with an increase in the pH(e) (DeltapH(e), approximately 0.2), whereas switching the perfusion solution from the NH(4)Cl solution to a 5% CO(2)/25 mM HCO(3)(-) solution produced a gradual increase in the EP to the control level with the concomitant recovery of the pH(e). (iii) The perfusion with a solution of high or low HCO(3)(-) with a constant CO(2) level within 10 min produced no significant changes in the EP. (iv) Perfusion of the perilymph with 10 microg/ml nifedipine suppressed the transient asphyxia-induced decrease in EP slightly, but not significantly. (v) By contrast, the administration of 1 microg/ml nifedipine via the endolymph inhibited significantly the reduction in the EP induced by transient asphyxia or perilymphatic perfusion with CO(2)/HCO(3)(-)-free or 20 mM NH(4)Cl solution. These findings suggest that the effect of CO(2) removal from perilymphatic perfusion solution on the EP may be mediated by an increase in cytosolic Ca(2+) concentration induced by an elevation of cytosolic pH in endolymphatic surface cells.

The influence of Er. YAG laser application in fenestration to the inner ear

Objective Erbium (Er.) YAG laser may be usable for middle ear surgery because of its ability to ablate bony tissue. We investigated the inner ear damage caused by the fenestration to the inner ear with Er. YAG laser. Design We investigated the influence of Er. YAG laser on the inner ear using electrophysiological technique. Results Several cases had a decrease in endocochlear potential (EP) and cochlear microphonics (CM) after the fenestration to the inner ear. Conclusions Er. YAG laser is safe if it is used for the small and superficial fenestration to the stapes footplate. However, a few extra pulses after fenestration are dangerous.

Endolymphatic Perfusion with EGTA-Acetoxymethyl Ester Inhibits Asphyxia- and Furosemide-Induced Decrease in Endocochlear Potential in Guinea Pigs

We examined the effect of the Ca(2+) concentration in the endolymph ([Ca](e)) or in the endolymphatic surface cells ([Ca](i)) on the endocochlear potential (EP) by using an endolymphatic or perilymphatic perfusion technique, respectively. (i) A large increase in [Ca](e) up to approximately 10(-3) M with a fall in the EP was induced by transient asphyxia ( approximately 2 min) or by the intravenous administration of furosemide (60 mg/kg), and a significant correlation was obtained between the EP and p[Ca](e) (= -log [Ca](e), r = 0.998). (ii) Perfusion of the endolymph with 10 mM EGTA for 5 min neither produced any significant change in the EP nor altered the asphyxia-induced change in EP (DeltaEP(asp)), suggesting that neither [Ca](e) nor the Ca(2+) concentration gradient across the stria vascularis contributed directly to the generation of the EP in the condition of low [Ca](e). In contrast, endolymphatic perfusion with high Ca(2+) (more than 10 mM) produced a decrease in EP and a significant correlation was obtained between the EP and the Ca(2+) concentration of perfusion solution (r = 0.982), suggesting that Ca(2+) permeability may exist across the stria vascularis. (iii) The administration of a Ca(2+) chelator, EGTA-acetoxymethyl ester (AM, 0.3 mM), to the endolymph, which produced a gradual increase in EP, suppressed significantly, by 60-80%, DeltaEP(asp) or furosemide-induced changes in EP. In contrast, perilymphatic administration of 0.5 mM EGTA-AM caused no significant suppression of the DeltaEP(asp). These findings suggest that [Ca](i) plays an important role in generating/maintaining a large positive EP.

Alterations in the stria vascularis in relation to cisplatin ototoxicity and recovery

We have investigated whether or not cisplatin-induced depression of the endocochlear potential (EP), and its subsequent recovery, possesses a morphological correlate in the stria vascularis. Guinea pigs implanted with round window electrodes were treated daily with cisplatin (1.5 mg/kg/day) until the compound action potential showed a profound hearing loss (≥40 dB at 8 kHz after 5–18 days). Animals were either sacrificed immediately after the shift in hearing threshold (‘SHORT’ group) or allowed to recover for ≥4 weeks and subsequently sacrificed (‘LONG’ group). Control animals (‘CONTROL’ group) were not treated with cisplatin. Using stereological methods we measured the total strial cross-sectional area together with the areas occupied by the different strial components: the marginal, intermediate and basal cells. The total strial cross-sectional area in the basal turn of the LONG group was found to be significantly smaller than that of the SHORT and the CONTROL groups, whereas the EP was normal in the LONG group (in comparison to the CONTROL group) and markedly decreased in the SHORT group. The smaller area in the LONG group was mainly due to a decrease in the area occupied by the intermediate cells and to a lesser extent to a decrease in the marginal cell area. The area occupied by the basal cells did not change. Thus, the marked decrease in EP after 5–18 days of cisplatin administration was not related to shrinkage of the stria vascularis. Moreover, 4 weeks later the EP showed full recovery, whereas the stria vascularis had shrunk markedly.

Effects of round window membrane rupture on cochlear blood flow and endocochlear potential

The degree of hearing loss and audiogram shape vary in patients with perilymphatic fistula. The cause of variability is not well known. To determine the effect of perilymphatic fistula on cochlear function, we studied the effect of round window membrane rupture on cochlear blood flow (CBF) by placing a laser-Doppler probe to the basal turn in 20 guinea pigs. In 10, endocochlear potential (EP) was measured by inserting a glass microelectrode through the stria vascularis of the basal turn. During 60 minutes following round window membrane rupture, CBF decrease of more than 15% was observed in 9 of 20 animals, and EP decrease of more than 15% was observed in 5 of 10. A significant correlation was observed between the degree of CBF reduction and EP reduction. In 3 animals in which CBF decreased after round window membrane rupture, temporal bones were studied histologically. One cochlea showed endolymphatic hydrops and another cochlea showed significant hemorrhage in the scala tympani after rupture. These results suggested that CBF impairment is associated with cochlear dysfunction in perilymphatic fistula.

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.

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 μl/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.

Changes in Off-lesion Endocochlear Potential Following Localized Lesion in the Lateral Wall

Endocochlear potential (EP) was measured at various off-lesion sites after a small focal lesion was made in the lateral wall of the guinea pig cochlea. Lesions were produced by a photochemical reaction between systemically administered rose bengal and focused green light illumination. In 21 ears, continuous measurement for 30 min after onset of the reaction at turns apical or basal to the site of illumination revealed no significant changes in EP compared with the control value (p<0.01). In another group of 43 ears, EP was measured at 3 days post-illumination. A significant decline was seen at every site located apical to the lesion (p<0.001). Conversely, no significant change was measured at any site located basal to the lesion. These findings suggest that the decrease in EP assumes the form of a gradient from the lower to upper turns in the guinea pig cochlea.

Effects of aging on potassium homeostasis and the endocochlear potential in the gerbil cochlea

Previous work has shown that the endocochlear potential (EP) decreases with age in the gerbil. Concomitant with the EP decrease is an age-related loss of activity of Na,K-ATPase in the lateral wall and stria vascularis. We hypothesized that the EP decrease is associated with a similar decrease in the endolymphatic potassium concentration [K e +]. This hypothesis was tested using double-barrelled, K +-selective electrodes introduced into scala media through the round window in young and quiet-aged gerbils. Results show that the means (±S.D.) of the [K e +] in young and aged gerbils were not significantly different (178.2 ± 14.2 mM and 171.2 ± 34.4 mM, respectively), although the intersubject variability was much greater in the aged animals than in the young. These values of [K e +] are slightly higher than those found for other mammals and may reflect the higher plasma osmolarity found in the gerbil. The concentration of perilymphatic potassium [K p +] in scala tympani at the round window was also similar for the young and aged groups (3.57 ± 1.17 mM and 4.18 ± 2.03 mM, respectively). On the other hand, mean EP values in the young and aged gerbils were 92.0 ± 5.7 mV and 64.8 ± 15.8 mV, respectively and were statistically different ( P < 0.001). Overall, EP and [K e +] showed little correlation ( R 2 = 0.23), except that when [K e +] fell below 150 mM, the EP was always less than 60 mV. An analysis of the chemical potential for K e + with respect to K p + shows that it was similar for young and aged gerbils (overall mean of 103.1 ± 13.7 mV) and remained constant with respect to the EP, in spite of an overall electrochemical potential of K e + that varied from 120 to 210 mV. Thus, the system maintains K e + homeostasis at the expense of the EP, even when the EP is on the verge of collapse.

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

エリスロマイシンのか牛電位への影響

The mechanism of hearing loss following administration of intravenous erythromycin lactobionate was investigated using the albino guinea pig. This hearing loss was found, for the first time, to be due to cochlear dysfunction caused by erythromycin administration.The endocochlear potential (EP) and the cochlear microphonics (CM), recorded at the first or second cochlear turn, transiently decreased when erythromycin was administered intravenously at dosages of 100 and 150 mg/kg. The decrease in EP and CM was clearly related to dose. A complete recovery of EP and CM ensued after each erythromycin application. However, perilymphatic perfusion with 3 mM of erythromycin caused an immediate and drastic decrease in CM, while it caused a mild decrease in EP following its initial elevation. The magnitude of the negativity of EP in response to anoxia was small after perilymphatic perfusion, while it remained within the normal range with intravenous application.These findings suggest that intravenously applied erythromycin has a direct effect upon the stria vascularis, while erythromycin applied via the perilymph exerts its potent action predominantly on the hair cells.

Effect of focal cochlear vascular lesion on endocochlear potential in guinea pigs

The alteration endocochlear potential (EP) in response to total cochlear ischemia induced by various experimental manipulations has been studied. However, the effect of restricted areal damage to the microvessels (restricted to small area in the lateral wall of a cochlear turn) on the EP value is still unknown. In the current investigation we adopted a photochemical method to produce a focal (i.e., restricted area) microvessel injury in the lateral wall of the guinea pig cochlea and examined the effect of these insults on EP recorded in the same region. The small area of the microvessel lesion (small fenestra: approximately 0.2 × 0.4 mm 2) induced by photoactivation did not yield significant EP changes, suggesting that damage to such a small area of microcirculation in the lateral wall of the cochlea has no statistically significant effects on EP values. In subjects with a large area of the microvessel lesion (large fenestra: ≈ 0.2 × 0.8 mm 2), a decrease in the EP value (mean ± SEM 7.9 ± 0.8 mV) was noted. However, the control group animals with a large fenestra but without microvessel lesion also displayed a decrease (8.6 ± 0.8 mV) in EP. In the current study we were unable to differentiate whether the EP changes in animals with the large fenestra microvessel lesions were caused by the cochlear blood flow decrease or by the surgical preparation. However, the results of this study indicated if the EP value was affected by the large area of the microvessel lesion, the level of decrease would not be large. That is, the EP decrease was less than the change in the control group (mean: 8.6 mV). Considering the dependence of EP on blood flow, the data of this study suggest that compensatory mechanisms in the cochlea may maintain the EP following a focal lesion in the lateral wall of the cochlea. This study also indicates that the photochemical method provides a reliable approach to produce the animal model with the focal microvessel lesion in the lateral wall of the cochlea.