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Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The most crucial clinical problem of Eosinophilic Otitis Media (EOM) is sensorineural hearing loss. A previous report revealed that repeated antigen stimulation of middle ear causes eosinophilic inflammation not only in the middle ear but also in the inner ear. Objective: The purpose of the present study was to elucidate the mechanism of eosinophil infiltration to the inner ear in the animal model of EOM. Methods: Continuous OVA stimulation to the middle ear of guinea pigs was performed for 7 days, 14 days, and 28 days. Histological observation was made for eosinophil infiltration and morphological change of the inner ear. Immunostaining for eotaxin and RANTES was performed to study immunoreactivity of those chemokines. Results: In the 7-day stimulation side, a few eosinophils were found in the scala tympani, without obvious morphological damage of the inner ear. Moreover, immunoreactivity of both eotaxin and RANTES was significantly higher in the OVA stimulation sides than control sides. For both eotaxin and RANTES, the number of immunopositive cells was significantly increased in the 14-day stimulation side over the 7-day stimulation side. Conclusions: Eotaxin and RANTES seem to play some important roles for the eosinophil infiltration in the middle and inner ear of model animal of EOM. [ABSTRACT FROM AUTHOR]

Conclusion:Seven-day administration of systemic steroids was more effective in preserving hearing for 12 weeks after cochlear implantation (CI) than a 3-day delivery. Objectives:To determine the effectiveness of extended delivery of systemic steroids to preserve hearing in guinea pigs after CI. Methods:Dexamethasone (4 mg/ml) was delivered parenterally via a mini-osmotic pump for either 3 or 7 days. A dummy CI electrode was inserted via cochleostomy approach in 8-week-old guinea pigs. Auditory thresholds were assessed from tone burst auditory brainstem responses (2, 8, 16, 24, and 32 kHz) at 1 day prior to CI, and 1, 4, and 12 weeks after implantation. Histologic evaluation of the cochleae was carried out. Results:No differences were observed in hearing thresholds among groups before CI. Significant hearing preservation was achieved at 8, 16, 24, and 32 kHz only in the 7-day infusion group compared with the control group at 1 week after CI. The same trend was maintained at 4 weeks (16, 24 kHz) and 12 weeks (16, 24, and 32 kHz). Histologic review of the 7-day infusion group revealed less fibrosis and ossification in the scala tympani and the preservation of more spiral ganglion cells, compared with the control group. [ABSTRACT FROM PUBLISHER]

ConclusionSuper paramagnetic nanoparticles (MNP) are a promising vector to achieve controlled drug delivery into the cochlea. ObjectiveThe goal of the study was to evaluate the toxicological risk of MNP upon the inner ear. MethodsFe3O4-MNP displacement was studied in various catheter materials, shape, and solvent with a local magnetic field. EC5V cells (derived from the inner ear) were cultured with MNP (100 and 500 nm) at various concentrations or without MNP. Cell survival was assessed with a flow cytometry analysis. Localization of MNP within the cells was studied with confocal microscopy.In vivo, a single intra-cochlear administration of 200 nm MNP (3 × 1010MNP/mL,n = 8; 1.5 × 1012MNP/mL,n = 6) or saline (n = 14) was performed in guinea pigs. Hearing thresholds were assessed with auditory brainstem responses at Day 7. ResultsMNP could be concentrated at different locations of the catheter with sequential activation of solenoids. MNP were internalized in the cytoplasm, but not in the nuclei nor in endosomes at 48 h. After 48 h of incubation, no difference for cell survival between the groups was observed, whatever the MNP concentration. A size effect was observed with less survival in the 100 nm group. In guinea pigs at day 7, hearing threshold shift was not different in the three groups. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Conclusion: The results of the study showed that clarithromycin has anti-inflammatory and antioxidant effects and, when it is combined with prednisolone, those effects gain strength. Objectives: The present study aims to investigate the effects that the antioxidant and anti-inflammatory activities of clarithromycin and/or prednisolone have on experimental otitis media in effusion-induced guinea-pigs. Method and results: In this study, 35-male guinea pigs were randomly divided into five-groups. For the experimental otitis media, intra-tympanic histamine (0.1 ml) was injected into the guinea pigs in all of the groups except the control group. Then, 24-h after the intra-tympanic injections, clarithromycin (15 mg/kg/day) and/or prednisolone (1 mg/kg/day) were applied intraperitoneally to the guinea-pigs for 7-days. The biochemical analysis showed an increase in antioxidant capacity and a decrease in oxidant status and malondialdehyde (MDA) levels in the clarithromycin group and the prednisolone group and especially in the clarithromycin+prednisolone group, as compared to the experimental group (p < 0.05). In the cytokine analysis, lower levels of interleukin (IL)-6 and IL-17A and higher IL-10 were found in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups than in the experimental group (p < 0.05). Furthermore, the histologic analyses showed histopathologic changes in the middle ear mucosa of the experimental group, but comparatively fewer-histopathologic changes were observed in the clarithromycin, prednisolone, and clarithromycin+prednisolone groups. [ABSTRACT FROM AUTHOR]

Conclusion: Polymer-coated electrodes can reduce surgically-induced trauma associated with the insertion of a cochlear implant (CI) electrode array. Objectives: To evaluate if insertion trauma in CI surgery can be reduced by using electrode arrays coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer. Methods: We analyzed characteristics of the Contour Advance® electrode arrays coated with MPC polymer. To assess surgical trauma during electrode insertion, polymer-coated or uncoated (n = 5 each) animal electrode arrays were implanted in guinea pig cochleae and operability and electrophysiological and histological changes were assessed. Results: Under light and scanning electron microscopy, polymer-coated electrodes did not appear different from uncoated electrodes, and no change was observed after mechanical stressing of the arrays. Electrode insertion was significantly easier when polymer-coated electrodes were used. Auditory brainstem response (ABR) thresholds did not differ between groups, but p1-n1 amplitudes of the coated group were larger compared with the uncoated group at 32 kHz at 28 days after surgery. The survival of outer hair cells and spiral ganglion cells was significantly greater in the polymer-coated group. [ABSTRACT FROM AUTHOR]

Conclusion: Programmed cell death (PCD) initially starts in the support cells (SCs) after electrode insertion trauma (EIT), followed by PCD in hair cells (HCs). Activation of caspase-3 was observed only in SCs. Protecting both SCs and HCs with selective otoprotective drugs at an early stage post implantation may help to preserve residual hearing. Objectives: Cochlear implant EIT can initiate sensory cell losses via necrosis and PCD within the organ of Corti, which can lead to a loss of residual hearing. PCD appears to be a major factor in HC loss post-EIT. The current study aimed to: (1) determine the onset of PCD in both SCs and HCs within the traumatized organ of Corti; and (2) identify the molecular mechanisms active within the HCs and SCs that are undergoing PCD. Methods: Adult guinea pigs were assigned to one of two groups: (1) EIT and (2) unoperated contralateral ears as controls. Immunostaining of dissected organ of Corti surface preparations for phosphorylated-Jun, cleaved caspase-3, and 4-hydroxy-2,3-nonenal (HNE) were performed at 6, 12, and 24 h post-EIT and for contralateral control ears. Results: At 6 h post-EIT the SCs immunolabeled for the presence of phosphorylated-Jun and activated caspase-3. Phosphorylated p-Jun labeling was observed at 12 h in both the HCs and SCs of middle and basal cochlear turns. Cleaved caspase-3 was not observed in HCs of any cochlear turn at up to 24 h post-EIT. Lipid peroxidation (HNE immunostaining) was first observed at 12 h post-EIT in both the HCs and SCs of the basal turn, and reached the apical turn by 24 h post-EIT. [ABSTRACT FROM AUTHOR]

Conclusions: No significant subepithelial healing differences were found between Gelfoam and polyurethane foam (PUF). However, levels of hyperplasia of the mucosal lining and inflammation were lower with PUF packing. PUF packing is not feasible as a middle ear packing material for abraded mucosa. Further studies are required before clinical application. Objective: To date, there have been few reports on the antiadhesive effect of PUF as a middle ear packing. The purpose of this study was to investigate the antiadhesive effect of PUF soaked with saline in an animal model of mucosal trauma. Methods: Bioresorbable PUF soaked with saline was placed over abraded mucosa in the experimental group ( n = 7), and compressed Gelfoam soaked with saline was placed in the control group ( n = 7). After measurement of auditory brainstem responses (ABRs), the animals were sacrificed 3 weeks after packing placement for histological observation. Results: The ABR results at postoperative week 3 showed no statistically significant difference between the preoperative and post-packing values. An adhesion pattern with subepithelial thickening was observed in the control group. Adhesion was not observed in the experimental group; however, subepithelial fibrous thickening was noted. [ABSTRACT FROM AUTHOR]

Conclusions: Human inner ear neurons have an innate regenerative capacity and can be cultured in vitro in a 3-D gel. The culture technique is valuable for experimental investigations of human inner ear neuron signaling and regeneration. Objectives: To establish a new in vitro model to study human inner ear nerve signaling and regeneration. Methods: Human superior vestibular ganglion (SVG) was harvested during translabyrinthine surgery for removal of vestibular schwannoma. After dissection tissue explants were embedded and cultured in a laminin-based 3-D matrix (Matrigel™). 3-D growth cone (GC) expansion was analyzed using time-lapse video microscopy (TLVM). Neural marker expression was appraised using immunocytochemistry with fluorescence and laser confocal microscopy. Results: Tissue explants from adult human SVG could be cultured in 3-D in a gel, indicating an innate potential for regeneration. Cultured GCs were found to expand dynamically in the gel. Growth cone expansion and axonal Schwann cell alignment were documented using TLVM. Neurons were identified morphologically and through immunohistochemical staining. [ABSTRACT FROM AUTHOR]

Conclusion: Our study demonstrates that the regulation of D2 receptors may be frequency specific. The reduction in cochlear microphonics (CM) and distortion product otoacoustic emission (DPOAE) amplitudes after perfusion with a D2 antagonist suggests that this receptor plays a role in the regulation of cochlear hair cell activation. Objectives: Dopaminergic terminals are subject to negative feedback from dopamine D2 receptors. In the present study we investigated whether the regulation of dopamine D2 receptor is frequency specific and evaluated changes in CM in guinea pig cochlea. Methods: A total of 30 male guinea pigs were randomly assigned to 3 groups and perfused with artificial perilymph (AP), AP containing ethanol (0.1%), or a D2 antagonist (L741626) for 2 h. In each group, compound action potentials (CAPs) evoked by a 1, 2, 4, 8, 16 or 24 kHz tone pip, CM evoked by 4 kHz tone bursts, and DPOAEs were measured before and 2 h after perilymphatic perfusion. Results: Perfusion with the D2 antagonist resulted in increased CAP thresholds compared with the other two groups at high frequencies (4, 8, 16, 24 kHz, p < 0.05); however, no significant increase was observed at low frequencies (1, 2 kHz, p > 0.05). There was a significant reduction in DPOAEs and CM amplitudes after the 2 h perfusion with the D2 antagonist. A CM input/output (I/O) function curve plotted with the stimulating level as input and the CM relative amplitude as output indicated obvious nonlinearity after the 2 h perfusion in all three groups. [ABSTRACT FROM AUTHOR]

Conclusion: Inhibition of thioredoxin reductase (TrxR) may be a contributing factor in cisplatin-induced ototoxicity. Direct exposure of organ of Corti to cisplatin and oxaliplatin gives equal loss of hair cells. Objectives: Platinum-containing drugs are known to target the anti-oxidant selenoprotein TrxR in cancer cells. Two such anti-cancer, platinum-containing drugs, cisplatin and oxaliplatin, have different side effects. Only cisplatin induces hearing loss, i.e. has an ototoxic side effect that is not seen after treatment with oxaliplatin. The objective of this study was to evaluate if TrxR is a target in the cochlea. Loss of outer hair cells was also compared when cisplatin and oxaliplatin were administered directly to the organ of Corti. Methods: Organ of Corti cell culture was used for direct exposure to cisplatin and oxaliplatin. Hair cells were evaluated and the level of TrxR was assessed. Immunohistochemical staining for TrxR was performed. An animal model was used to evaluate the effect on TrxR after treatment with cisplatin and oxaliplatin in vivo. Results: Direct exposure of cochlear organotypic cultures to either cisplatin or oxaliplatin induced comparable levels of outer hair cell loss and inhibition of TrxR, demonstrating that both drugs are similarly ototoxic provided that the cochlea becomes directly exposed. [ABSTRACT FROM AUTHOR]

Conclusion: As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss. Objective: The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed. Methods: We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study. Results: In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed. [ABSTRACT FROM AUTHOR]

Conclusion: Autoclaving the ossicles for 4 min at 134°C impacts superficial devitalization and elimination of the squamous epithelium on the surface of the ossicles. Bone maintains the integrity, firmness, and lamellar structure and ossicles are integrated into the middle ear without any adverse reactions. Objective: Sixteen guinea pigs were used to explore the effect of autoclaving on middle ear ossicles. Methods: Harvested incudomallear complex was autoclaved for 4 min at 134°C and implanted back into the middle ear cavity. Exploration of the middle ear was carried out 30 days after implantation. Results were compared with a control group of 16 non-autoclaved ossicles. Results: Autoclaved ossicles maintained their integrity, firmness, shape, and lamellar structure with Haversian systems. Autoclaving substantially decreased the vitality of the ossicles. The middle ear mucosa overgrew on the ossicular surface. No adverse reactions of soft tissue against ossicles occurred. Although the autoclaved ossicles were implanted with tympanic membrane (squamous epithelium) the histological examination did not demonstrate any residuum of squamous epithelium. In the control group we proved the presence of squamous epithelium on the manubrium surface in all cases; all ossicles were vital without signs of ostitis. [ABSTRACT FROM AUTHOR]

Conclusion: rAAV-NT4-ADNF-9 could ameliorate the damage to auditory function and repair previous impairment of cochlear hair cell loss induced by kanamycin. Objective: To investigate the therapeutic effect of ADNF-9 on cochlear hair cells using the recombinant adeno-associated virus (AAV) carrying fusion gene NT4-ADNF-9 and the kanamycin-deafened guinea pig model. Methods: Forty white guinea pigs with normal auricle reflex and normal auditory brainstem responses (ABRs) were randomly divided into four groups. Kanamycin was administered to the animals in groups A, B, and C to establish the deafened guinea pig model. rAAV-NT4-ADNF-9, vector only, and artificial perilymph were then delivered to the cochlear tissue of animals in groups A, B, and C, respectively, through the round window membrane. Animals in group D did not receive any treatment and acted as normal controls. The hearing thresholds on the surgery side were recorded before and after the transfection treatment. Fourteen days after treatment, cochleae were removed for paraffin slide preparation and cochlear surface preparation. A phase contrast microscope was used to observe the protective effect of ADNF-9 on hair cells. Results: Significant reduction of the ABR threshold was observed after rAAV-NT4-ADNF-9 treatment ( p < 0.05). After 14 days of treatment, the ABR threshold was also significantly different between the rAAV-NT4-ADNF-9-infected group and the non-infected group. Moreover, phase contrast microscopy showed significantly less hair cell damage or hair cell loss in the group treated with rAAV-NT4-ADNF-9 than in the groups treated with vector only or artificial perilymph ( p < 0.05). [ABSTRACT FROM AUTHOR]

Conclusion: Administration of diluted solutions of gadoteridol might cause considerably less toxic effects on cochlear outer hair cells (OHCs). Objectives: Visualization of endolymphatic hydrops is done by intratympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. Here, we investigated the physiological and morphological responses of guinea pig cochlear cells to gadoteridol. Methods: Distortion product otoacoustic emission (DPOAE) levels were measured before and 1, 2, and 4 weeks after intratympanic injection of 1/8 or 1/16 dilution of gadoteridol in guinea pigs. Morphological changes in isolated cochlear OHCs were observed after application of gadoteridol and GdCl3. Results: At the highest frequency (F2 = 12 000 Hz), DPOAE level was significantly ( p < 0.05) lower in the 1/8 diluted gadoteridol group than in the control group. Cell shape changes were observed in 24% (6/25) and 3% (1/33) of OHCs after application of 1/8 and 1/16 diluted gadoteridol, respectively. The occurrence of morphological damage was significantly lower after application of saline compared with 1/8 diluted gadoteridol. Morphological damage was significantly lower after application of 1/16 diluted gadoteridol compared with 1/8 diluted gadoteridol ( p < 0.05). Morphological damage was observed at a high rate (8/10 cells, 80%) after application of GdCl3. [ABSTRACT FROM AUTHOR]

Conclusion: The curative effect in the group where facial-facial anastomosis (FFA) was delayed for 7 days was similar to that in the immediate FFA group and had a better repair within 60 days. Objective: Due to the uncertainty about optimal timing of delayed facial nerve repair, we designed an experimental study in guinea pigs to find out the cut-off duration for delayed nerve repair. Methods: In this study, 64 male guinea pigs were randomly divided into 8 groups: normal, immediate FFA, and delayed FFA for 7, 14, 21, 30, 60, and 90 days ( n = 6). Two months after suture of the nerves, the passing rate of myelinated fibers growing from the proximal to the distal stumps was calculated. Results: The passing rates of myelinated fibers in the groups with immediate FFA and FFA delayed for 7 days were significantly higher than those in other delayed FFA groups and the difference was statistically significant ( p < 0.05), whereas the passing rates of the groups where FFA was delayed for 60 and 90 days were apparently lower than those of the immediate FFA and other delayed FFA groups. Under the electron microscope, regenerated fibers of the groups with immediate FFA and FFA delayed for 7 days were very similar to the normal myelinated fibers. [ABSTRACT FROM AUTHOR]

Conclusions: Systemic desmopressin (dDAVP) administration in guinea pigs for up to 2 weeks induced only minor or no significant changes in cochlear sensitivity, suggesting that other factors may be required to induce the cochlear dysfunction that is usually associated with endolymphatic hydrops. Objectives: To investigate the effects of chronic systemic administration of dDAVP, a synthetic analog of vasopressin, on cochlear sensitivity in guinea pigs. Methods: dDAVP was administered subcutaneously via a mini-osmotic pump, at a rate of 0.2 ng/kg/min (low-dose group) or 2.0 ng/kg/min (high-dose group) for up to 2 weeks. Cochlear responses (compound action potentials) and distortion product otoacoustic emissions (DPOAEs) were measured. Example specimens were scanned using X-ray micro-tomography (micro-CT). Results: Compared with the control group, the low-dose dDAVP group showed a significant threshold increase in response to a 2 kHz tone-burst after 2 weeks of treatment, and also a decrease in the amplitude of the DPOAE after 1 week of treatment. However, individual results were variable and the high-dose dDAVP group showed no significant change compared to the control group. In the micro-CT images, two of four ears in the low-dose group showed mild hydrops, but no hydrops was found in the three ears sampled from the high-dose group. [ABSTRACT FROM AUTHOR]

Conclusion: Dexamethasone provides protection against noise-induced hearing loss (NIHL) possibly by suppressing cochlear Hes1 expression via a glucocorticoid receptor (GR)-dependent mechanism. Objectives: The purpose of the present study was to explore whether hairy and enhancer of split 1 (Hes1) was involved in the protective effect of dexamethasone against NIHL. Methods: Guinea pigs, which were administered intraperitoneal injections of either saline, 1.0 mg/kg dexamethasone, 20.0 mg/kg RU38,486, or a combination of both drugs (dexamethasone plus RU38,486) for 5 consecutive days, were exposed to white-band noise (115 dB sound pressure level). The expression level of Hes1 in cochleae was compared using real-time RT-PCR and Western blot analysis. Results: Noise exposure for 3 h induced auditory brainstem response (ABR) threshold elevations, outer hair cell losses, and increase of Hes1 expression. Dexamethasone pretreatment prevented the NIHL with decreased Hes1 expression, which could be blocked by GR antagonist RU38,486. [ABSTRACT FROM AUTHOR]

Conclusion: The use of both gadolinium chloride (GdCl3) and osmium tetroxide (OsO4) allowed for the visualization of the membranous labyrinth and other intralabyrinthine structures, at different intensities, as compared with the control sample. This initial comparison shows the advantages of GdCl3 in radiological assessments and OsO4 in more detailed anatomical studies and pathways of labyrinthine pathogenesis using X-ray microtomography (microCT). Objective: To assess an improved OsO4 staining protocol and compare the staining affinities against GdCl3. Methods: Guinea pig temporal bones were stained with either GdCl3 (2% w/v) for 7 days or OsO4 (2% w/v) for 3 days, and scanned in a microCT system. The post-scanned datasets were then assessed in a 3D rendering program. Results: The enhanced soft tissue contrast as presented in the temporal bones stained with either GdCl3 or OsO4 allowed for the membranous labyrinth to be visualized throughout the whole specimen. GdCl3-stained specimens presented more defined contours of the bone profile in the radiographs, while OsO4-stained specimens provided more anatomical detail of individual intralabyrinthine structures, hence allowing spatial relationships to be visualized with ease in a 3D rendering context and 2D axial slice images. [ABSTRACT FROM AUTHOR]

Conclusion: Acellular dermal matrix (ADM) can be used as a substitute for tympanic membrane (TM) reconstruction. Objective: To investigate the effectiveness of ADM in the treatment of TM perforations. Methods: Fifty guinea pigs were used to create TM perforations. The perforations of the left TM were repaired with ADM by patch technique in 28 guinea pigs and by underlay technique in 22 guinea pigs. The right ears were used as the control group by establishing TM perforation but without TM reconstruction. The morphological and structural status of the grafts was observed by immunohistochemistry and scanning electron microscopy. Results: There was no statistically significant difference in TM perforation closure between the ADM patch technique group and the ADM underlay technique group, but these groups had a higher success rate in closing TM perforation than the control group. The healed TMs with ADM had the same characteristics as normal TM on histological examination. [ABSTRACT FROM AUTHOR]

Conclusion: Dexamethasone released from a cochlear implant seems not to enhance the risk for postoperative infections. Objective: Dexamethasone has a positive impact on hearing preservation for electric acoustic stimulation (EAS). Due to their antiproliferative and immunosuppressive properties, steroids may enhance the risk of postoperative infections. A comparative study was performed to evaluate the risk of pneumococcal meningitis after implantation of dexamethasone-eluting cochlear implants. Methods: Thirty guinea pigs were implanted with non-eluting ( n = 15) or dexamethasone-eluting ( n = 15) cochlear implant electrode dummies. After 5 weeks, animals were exposed to a virulent strain of Streptococcus pneumoniae. The two groups were compared based on the meningitis rate. Animals were observed for 5 days for signs of meningitis. Meningitis was verified by clinical outcome as well as by pleocytosis and presence of bacteria in cerebrospinal fluid. Results were confirmed by histological examination of brains and cochleae, clinical findings and culture. Results: There was no significant difference in meningitis risk between the two groups. In the group with non-eluting implants, 3 of 15 animals developed meningitis, while in the group with dexamethasone-eluting implants 4 of 15 showed signs of meningitis. In this study dexamethasone-releasing implants did not significantly increase the risk of postoperative pneumococcal otogenic meningitis. [ABSTRACT FROM AUTHOR]

Conclusions: Both nifedipine and noise exposure had damaging effects on cochlear function. These damaging effects were subtractive rather than additive, suggesting that calcium channel blockers may have a protective role in noise-induced hearing loss. Objective: We assessed the interaction of nifedipine, a calcium channel blocker, with noise in cochlear function by evaluating changes in the compound action potential (CAP) threshold after the administration of nifedipine with or without noise exposure. Methods: Eighty guinea pigs were randomly assigned to eight groups based on those with cochlear perfusion with nifedipine only (0, 0.15, 0.5, and 3 µM, groups 1-4) and noise exposure (groups 5-8). CAP thresholds were recorded using a round window electrode before and 120 min after cochlear perfusion. Results: Cochlear perfusion of different concentrations of nifedipine caused 2.5, 5.5, 28, and 21.5 dB SPL threshold shift, respectively, at 0, 0.15, 0.5, and 3 µM concentrations (groups 1-4). In comparison, the CAP thresholds after nifedipine perfusion with noise exposure were 43.5, 46.5, 20, and 21.5 dB SPL, respectively, in groups 5-8. [ABSTRACT FROM AUTHOR]

Conclusion: The excessive glutamate released from the type I and type II hair cells and the supporting cells injure the bouton-type endings and the nerve chalices in 30 min ischemia, and neuronal damage of glutamate was slight in 10 min ischemia. Objective: In the present study, we investigated by means of post-embedding immunoelectron microscopic analysis whether neuronal damage in the vestibular end organs is associated with the change of cellular glutamate concentration during ischemia. Methods: Transient local anoxia (10 min, 30 min) of guinea pig inner ear was induced by pressing the left labyrinthine artery. The right sides were used as controls. The morphological changes of the vestibular end organs and the areal gold particle densities representing glutamate were compared in the ischemia side and the control side. Results: The areal gold particle densities of the type I and type II hair cells and the supporting cells in the ischemic side were lower than those of the control side. There were no remarkable morphological changes compared to the control side in 10 min ischemia. In 30 min ischemia, the bouton-type endings were swollen and intercellular spaces between the type I hair cells and the nerve chalices were enlarged. [ABSTRACT FROM AUTHOR]

Conclusion: The results suggest that the beneficial effect of astragaloside IV on impulse noise-induced hearing loss may be due to its ability to inhibit reactive oxygen species (ROS) and prevent apoptosis. Objective: Astragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of diseases in China for its antioxidant properties. ROS and apoptosis are involved in damage induced by impulse noise trauma. We aimed to investigate if the beneficial effects of astragaloside IV on cochlea exposed to impulse noise are associated with the inhibition of ROS and the decrease in apoptosis. Methods: 4-Hydroxynonenal (HNE) was used as the marker of ROS. Active-caspase−3 (cas-3) served as a marker for apoptosis. 4HNE and cas-3 were determined immunohistochemically. Guinea pigs in the experimental group were administered astragaloside IV intragastrically. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) 72 h before and after exposure to impulse noise. Results: The results showed that astragaloside IV significantly reduced ABR deficits, and decreased the expression of ROS and cas-3. [ABSTRACT FROM AUTHOR]

Conclusions: The results suggest that melanin inhibits formation of reactive oxygen species (ROS) and prevents apoptosis in spiral ganglion cells (SGCs) of pigmented guinea pigs following impulse noise. Objective: The stria vascularis of pigmented guinea pig cochlea contains melanocytes that produce melanin, which has a protective effect on noise-induced hair cell damage through its antioxidant property. ROS are involved in cochlear damage induced by impulse noise trauma. The purpose of the present study was to investigate the oxidative stress in SGCs of pigmented and albino guinea pigs after exposure to impulse noise. Methods: Pigmented and albino guinea pigs were exposed to impulse noise. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) before impulse noise exposure and 72 h after impulse noise exposure. 4-Hydroxynonenal (HNE) was used as a histochemical marker of ROS formation, and active-caspase-3 (cas-3) served as a marker for apoptosis. 4-HNE and cas-3 were determined immunohistochemically. Hair cell damage was analyzed by scanning electron microscopy. Results: The rates of 4-HNE-positive and cas-3-positive SGCs in pigmented guinea pigs were much less than those for albino guinea pigs. Correspondingly, there was less hair cell damage and reduced ABR threshold shifts in pigmented guinea pigs. [ABSTRACT FROM AUTHOR]

Conclusion: The findings from this study extend the use of the local application of D-methionine (D-met) to protect against acoustic trauma and demonstrate that D-met slowly diffuses from the perilymph. Objectives: The objectives of the study were to determine the effect of D-met on auditory function and morphology after acoustic trauma and to measure the concentration of D-met in perilymph. Methods: Auditory thresholds were determine before, immediately after, and 24 h after acoustic trauma. Cochleae were analyzed using immunocytochemistry for c-Fos, TUJI, and cytochrome c. The concentration of D-met was determined from perilymph. Results: Protection against acoustic trauma (immediately and 24 h post trauma) on auditory brainstem thresholds was found at a time when the concentration of D-met in perilymph showed a fivefold increase above basal levels. The local application of D-met to the guinea pig cochlea results in elevated D-met concentrations that are maintained in the perilymph for at least 24 h. [ABSTRACT FROM AUTHOR]

Conclusion. These results suggest that the beneficial effect of astragaloside IV on impulse noise-induced hearing loss may be due to its ability to inhibit inducible nitric oxide synthase (iNOS) and prevent the formation of reactive nitrogen species (RNS). Objective: Astragaloside IV is the major active constituent of Astragalus membranaceus, which has been widely used for the treatment of diseases in China due to its antioxidant properties. iNOS and RNS are involved in damage induced by impulse noise trauma. The purpose of the present study was to investigate if astragaloside IV has the potential to reduce cochlear damage from impulse noise. Methods: Guinea pigs in the experimental group were administered astragaloside IV intragastrically. Auditory thresholds were assessed by sound-evoked auditory brainstem response (ABR) at click and tone bursts of 8, 16 and 32 kHz, 72 h before and after exposure to impulse noise. iNOS and nitrotyrosine were determined immunohistochemically. Hair cell damage was analyzed by scanning electron microscopy. Results: Astragaloside IV significantly reduced ABR deficits, reduced hair cell damage, and decreased the expression of iNOS and RNS formation. [ABSTRACT FROM AUTHOR]

Conclusion: Preventing leakage of endolymph during vestibular destruction may be important in the acute phase. Objectives: Vestibulotomy causes significant decrease in the endocochlear potential (EP). The effect of artificial perilymph and distilled water administration during vestibulotomy on hearing preservation was evaluated in Hartley guinea pigs. Methods: Animals were divided into three groups: the epitympanic bulla was filled with artificial perilymph or distilled water, or was not filled with any solution (control group). The EP and [K++] were monitored using double-barrelled ion-selective microelectrodes in the second turn of the cochlea. Results: EP was not significantly different between the artificial perilymph and the distilled water groups, although both groups showed better preservation of EP compared with the control group. The [K++] was not significantly different between the three groups. [ABSTRACT FROM AUTHOR]

Conclusion: Delivery of intramuscular injection of methylprednisolone around the implantation surgery improved the hearing threshold shift induced by cochlear implantation. Objectives: During electroacoustic cochlear implantation surgery, the residual hearing is not preserved in about 15% of cases. In this study, we tested the effects of intramuscular administration of methylprednisolone on the hearing loss induced by cochlear implantation in a model of guinea pig cochlear implantation. Methods: Eleven guinea pigs with normal hearing were implanted with a 254 μμm diameter silicone array through a cochleostomy, and the effects on hearing of longstanding array insertion (21 days) were assessed. Six of the implanted animals received intramuscular administration of methylprednisolone. Auditory brainstem response recordings were performed before and up to 21 days after the cochlear implantation. CT scans were performed in some animals 1 month after implantation. Results: CT scans confirmed that the array was well positioned in tested animals. From days 3 to 21, a hearing loss of about 30 dB on all frequencies was observed in the implanted nontreated group. This hearing loss remained stable during the whole follow-up period. Compared with implanted nontreated animals, the hearing threshold shift decreased by 12 dB in animals treated with methylprednisolone. [ABSTRACT FROM AUTHOR]

Conclusion: Our results are in agreement with the general idea that natural antioxidants achieve their best cytoprotective capacity if given before and soon after the stressor. Objective: We focused on ferulic acid (FA, 4-hydroxy 3-methoxycinnamic acid), a phenolic compound that is known to exhibit antioxidant properties. Our study was designed to evaluate the effectiveness of FA for different schedules of treatment to establish the ''therapeutic window'' for FA protection. Methods: Guinea pigs were exposed to acoustic trauma (6 kHz at 120 dB for 60 min) and received a total dose of 600 mg/kg of FA. Group I, noise control; group II, noise ++ FA (150 mg/kg) for 4 days starting 24 h post exposure; group III, noise ++ FA (60 mg/kg) 1 h before and 9 days post exposure; group IV, noise ++ FA (60 mg/kg) given 3 days before and 7 days post exposure; group V, noise ++ FA (150 mg/kg) 1 h before and 3 days post noise exposure. Auditory brainstem response (ABR) test and immunohistochemical and morphological studies were performed. Results: Group V had significantly decreased noise-induced hearing loss at day 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress marker. The other schedules of drug administration showed a minor degree of protection. [ABSTRACT FROM AUTHOR]

Conclusion: The degree of contrast enhancement of the cochlea after intratympanic administration of meglumine gadopentetate (Gd-DTPA) or gadodiamide hydrate (Gd-DTPA-BMA) varies widely among patients with inner ear diseases. There was no morphological change in the stria vascularis after Gd-DTPA or Gd-DTPA-BMA was placed on the round window of guinea pigs. Objectives: We investigated the degree of contrast enhancement of the inner ear after intratympanic administration of ionized and nonionized gadolinium (Gd) contrast agents in patients with inner ear diseases. The inner ear toxicities of these agents were investigated in guinea pigs. Methods: 3D-FLAIR MRI was conducted 1 day after the intratympanic injection of eightfold-diluted Gd-DTPA or Gd-DTPA-BMA in 73 patients with inner ear diseases. Gd enhancement of the basal turn of the cochlea was evaluated as the signal intensity (SI) ratio between the affected and nonaffected sides. In guinea pigs, nondiluted Gd-DTPA, Gd-DTPA-BMA or saline was placed on the round window for 1 h and the stria vascularis was observed using electron microscopy. Results: The SI ratio ranged from 1.5 to 16.5 in the Gd-DTPA group and from 2.5 to 21 in the Gd-DTPA-BMA group. Electron microscopy showed no significant differences in the stria vascularis of guinea pigs in any of the groups. [ABSTRACT FROM AUTHOR]

Conclusion: Excess glutamate (Glu) exposure (20 mM) in the cochlear perilymph affects the physiological function of outer hair cells (OHCs) within a 2 h period and induces apoptosis in the modiolus spiral ganglion neurons (SGNs) in an apoptosis-inducing factor (AIF)-dependent manner. Objectives: To determine whether high-dose Glu affects the function of OHCs and whether it induces AIF- and caspase-3-dependent apoptosis in the cochlear SGNs. Methods: Perilymphatic perfusions of Glu (20 mM) and artificial perilymph (AP) solutions were performed in adult guinea pig cochleae. Both cochlear microphonics (CM) and electrical auditory brainstem response (eABR) were measured before and 2 h after perfusions. The hair cell morphologies were examined using transmission electron microscopy. The expression of two apoptotic indicators, AIF and caspase-3, was examined 8 h after perfusions. Results: In contrast to AP perfusions, the perfusion of 20 mM Glu caused significant reduction in the CM and eABR amplitudes. Inner hair cells (IHCs) after Glu perfusion were deformed and exhibited vacuolization in the postsynaptic region, whereas the OHC system appeared unaffected. AIF expression was detected in the nuclei of SGNs 8 h after Glu exposure, but the expression of caspase-3 was not shown in any cochlear tissues. [ABSTRACT FROM AUTHOR]

Conclusion: Reactive oxygen species (ROS) and the c-Jun N-terminal kinase (JNK) signaling pathway may be involved in secondary apoptosis of spiral ganglion cells (SGCs) induced by intracochlear gentamicin injection. Objectives: The purpose of this study was to ascertain the role of ROS and the JNK signaling pathway in secondary apoptosis of SGCs induced by intracochlear gentamicin treatment. Methods: Gentamicin (40 mg/ml) was injected into the cochlea of guinea pigs ( n = 18) to destroy the hair cells and induce secondary apoptosis of SGCs. At 1 ( n = 6), 2 ( n = 6), and 3 ( n = 6) weeks after gentamicin treatment, the cochleas were removed and stained with hematoxylin and eosin, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling to observe the morphologic changes and apoptosis of SGCs. A dihydroethidium (DHE) assay was performed to detect ROS generation, and RT-PCR and Western blot analysis were used to assess the expression of Fas ligand (FasL), JNK, and c-Jun. Results: After gentamicin was injected into the cochlea, apoptosis and progressive loss of SGCs were observed. RT-PCR and Western blot analysis showed increased expression of FasL after gentamicin treatment. ROS generation detected by DHE fluorescence increased progressively, and the expression of JNK, phospho-JNK, c-Jun, and phospho-c-Jun also increased. [ABSTRACT FROM AUTHOR]

Objectives:The authors would like to confirm a fluid pathway from the scala tympani to the organ of Corti, and to observe its morphological changes. Methods:A staining solution for succinic dehydrogenase was perfused with phenazine methosulfate in the scala tympani of living guinea pigs (n = 5) under deep anesthesia. After fixation, the cochleas were eventually embedded in epon. Sections were observed under a light microscope. Results:Blue-stained tissue is indicative of the pathway taken by the solution. The staining solution entered the organ of Corti through Hensen-Deiters’ slit. The slit widened and Hensen’s cells were pushed laterally. A new space was formed medial to Hensen’s cells. Cortilymphatic hydrops developed. Conclusion:The Hensen-Deiters’ slit is a pathway of a certain staining solution from the scala tympani to inside the organ of Corti of the guinea pig. The influx of the fluid pushes Hensen’s cells laterally and upward, resulting in a formation of hydrops of the organ of Corti or cortilymphatic hydrops. The hydrops is observed in animals with experimental perilymphatic fistula and with viral labyrinthitis. At the end stage of the hydrops, only the surface of the organ of Corti remains as a thin layer without any cellular elements. [ABSTRACT FROM PUBLISHER]

Conclusion: Local application of hepatocyte growth factor using biodegradable gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs. Objectives: To develop an inner ear drug delivery system using gelatin hydrogels that is capable of a sustained delivery of growth factors to the cochlea. We examined the efficacy of the local application of gelatin hydrogels containing hepatocyte growth factor (HGF) in protecting cochlear hair cells from noise-induced damage. Materials and methods: A piece of gelatin hydrogel previously immersed in either HGF or saline was placed on the round window membrane of a guinea pig 1 h after noise exposure (4 kHz octave band noise at 120 dB sound pressure level for 3 h). Auditory function was monitored using auditory brainstem responses (ABRs), and the loss of hair cells was evaluated quantitatively. Results: Local HGF treatment significantly reduced the noise exposure-caused ABR threshold shifts and the loss of outer hair cells in the basal portion of the cochleae. [ABSTRACT FROM AUTHOR]

Conclusion. Our findings indicate that oxidative stress induces morphological changes in vestibular hair cells and subsequently leads to cell death after 2.5 h. Objectives. The aim of this study was to confirm the direct effects of oxidative stress on vestibular hair cells. Materials and methods. Vestibular hair cells isolated from guinea pigs were loaded with 1 or 10 mM H2O2, and morphological changes were observed. In addition, in a viability/cytotoxicity assay system, the numbers of dead cells in isolated cristae ampullares were counted 1, 3, and 5 h after loading with H2O2 or artificial perilymph (control). Results. Reactive oxygen, in the form of H2O2, directly affects the cell membrane of isolated vestibular hair cells and causes swelling of the cell body, bleb formation, and shortening of the neck region. Morphological changes occur within 30 min after loading with H2O2, but a significant increase in the number of dead cells is noted only after 3 h. [ABSTRACT FROM AUTHOR]

Objective Previous studies of the microvascular bed of the rat inner ear showed vascular constriction after i.v. application of endothelin-1 (ET-1). Luminal narrowing together with multiple circumscribed constrictions were observed on vascular corrosion casts of initial and small calibre veins. These constrictions were interpreted as being caused by contractile cytoplasmic fibrils, most probably of pericytes; pericytes reportedly respond to ET-1 and the frequency, distribution and dimension of pericytes and their cytoplasmic processes closely corresponded to the constrictions observed. In the present study we analysed the distribution of actin and myosin in order to directly show the presence of contractile cytoplasmic fibrils. Material and Methods We performed standard immunostaining for actin, smooth muscle actin, smooth muscle myosin and tropomyosin in the cochlea. We used different fixation protocols (methacarn, neutral formalin, Bouin's fluid) and compared observations in two species (rat and guinea pig). Results Immunohistochemistry confirmed the presence of contractile cytoplasmic fibrils in cochlear pericytes and vascular smooth muscle cells. Microvessels in the cochlea were much better provided with contractile fibrils in rats compared to guinea pigs. The distribution of contractile fibrils in rats corresponded well to the luminal constrictions observed on vascular corrosion casts. Conclusions Our results support the assumption that active myofibrillar contraction (in response to ET-1 stimulation of pericytes) causes luminal constriction in cochlear microvessels. Contraction of myofibrils can be influenced by intrinsic or extrinsic agents, which offers new therapeutic regimens to govern cochlear blood flow. As the frequency of contractile cells on cochlear microvessels varied with the species studied, evaluation of human material will be the next step. [ABSTRACT FROM AUTHOR]

Objective—To investigate the effect of cisplatin administration on the ultrastructural morphology of the organ of Corti, stria vascularis and spiral ganglion. Material and Methods—Forty-eight guinea pigs were treated with cisplatin by daily i.p. injection at a dose of 1.5 mg/kg for eight consecutive days. Electrocochleography was performed at various survival times after the final application of cisplatin. The cochleae were subsequently examined using electron microscopy. Results—Ultrastructural examination corroborated that, in cochlear turns showing complete loss of outer hair cells (OHCs) at the light microscopic level, OHCs were indeed missing and had been completely replaced by supporting cells. OHC loss, the number of affected OHCs and the degree of intracellular pathology in the OHCs in the 1-day, 1-week and 2-week survival groups were considerably higher than in the 4- and 8-week survival groups. All degenerated OHCs demonstrated ultrastructural features commonly associated with necrosis. No morphological signs of apoptosis were observed. Strial changes consisted of protrusion of the apical membrane of the marginal cells into the scala media, without any other histopathological changes. Intermediate-cell atrophy, apparent as translucent areas at the light microscopic level, consisted of an increase in intercellular space due to shrinkage of intermediate and marginal cells ultrastructurally. Ultrastructural examination of the spiral ganglion showed that vacuolation of the spiral ganglion cells, seen at the light microscopic level, was due to severe swelling of the mitochondria. Conclusion—The present results corroborate our previous light microscopic findings. However, the ultrastructural results do not allow a conclusion to be drawn concerning whether the observed recovery is due to the formation of new OHCs or to (self-)repair of damaged OHCs, although the latter is less likely. [ABSTRACT FROM AUTHOR]

Objective—Multiple patches of atrophy have been reported in the stria vascularis (SV) in elderly persons with presbycusis. The aim of this study was to investigate the correlation between sensorineural hearing loss and this strial condition. Material and Methods We established a new animal model comprising two small lesions in the SV in the second turn of the cochlea by means of photochemical reaction. Using this model, we investigated morphological and physiological changes in the cochlea at 3, 7 and 14 days after SV damage. Results—Scanning electron microscopy studies revealed that the strial cells between the two damaged areas of the SV remained intact, although the outer hair cells (OHCs) facing the intact SV area were damaged. Furthermore, damage to the first and second rows of OHCs gradually progressed throughout the 14-day observation period. The endocochlear potential (EP) measured at a point midway between the 2 lesions at 3 and 7 days was found to be significantly lower compared with control values, but had returned to a normal level at 14 days. Conclusion—The reversible EP change and localized OHC loss seen in the present investigation may help to understand acute idiopathic or progressive sensorineural hearing loss. [ABSTRACT FROM AUTHOR]