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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.)

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]

Conclusion: The ovariectomy in rats does not change their auditory function. However, combining ovariectomy with Cisplatin treatment increases the risk of damaging the auditory function relative to the ototoxic effect caused by Cisplatin alone or ovariectomy alone. Objectives: The auditory benefit from estrogen depends on a number of factors that make findings among studies controversial. The present study was to examine the impact of Cisplatin, a chemotherapy drug, on the auditory function of ovariectomized rats. Methods: Thirty-two female rats were assigned to three groups (OVX + C, OVX − C, Sham + C). The rats in the OVX + C and OVX − C groups received bilateral ovariectomy, and those in the Sham + C group received a sham surgery with intact ovaries. After 6 weeks the rats in the OVX + C and Sham + C groups were then treated with Cisplatin for 4 days, but not those in the OVX − C group (control). The auditory function was measured with DPOAE SNRs and ABR thresholds before the surgery and after the Cisplatin treatment. Results: The OVX + C group had significantly decreased the DPOAE SNRs and increased the ABR thresholds relative to the Sham + C group at stimulus frequencies between 2–8 kHz, and the Sham + C group also had worse auditory function than the OVX − C group. [ABSTRACT FROM AUTHOR]

Conclusion: Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. Objective: To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. Materials and methods: This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Results: Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally. [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.)

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: Clinical trials of cell-based therapies using induced pluripotent stem (iPS) cells have already been started for several neurological diseases. Objective: The purpose of the present study was to explore the characteristics and differentiation of somatic cells in vitro undergoing a low pH treatment, so as to provide new therapeutic strategies for treating sensorineural hearing loss. Methods: Somatic cells were treated with low pH solution to alter their characteristics. In addition, a mouse model of the cochlear lesion was constructed using bilirubin. Subsequently, the characteristics and therapeutic effect of somatic cells undergoing low pH treatment were examined by morphology, alkaline phosphatase (AKP) activity, immunofluorescence assay and q-PCR. Results: The cells in the experimental group grew better than those in the control group. The AKP activity in the experimental group was higher than that in the control group. The expression of Nanog and Oct4 was both positive in the two groups. When the cells were changed to neurobasal medium, the marker of nestin was positive. Conclusion: The human somatic cells undergoing a low pH treatment showed the similar characteristics as those of iPS cells, although the functions and therapeutic effect of these altered human somatic cells need to be further studied. [ABSTRACT FROM AUTHOR]

Conclusion: The auditory brainstem response (ABR) wave I threshold, latency and amplitude are insensitive to spiral ganglion neurons (SGNs) degeneration, but are sensitive to the degeneration of Schwann cells and can estimate the status of Schwann cells in a neural degeneration mouse model. The thorough pre-operative ABR assessment would be helpful in predicting cochlear implant performance. Objectives: This study aimed in finding a non-invasive electrophysiological method to evaluate the status of the auditory nerve and the Schwann cells in sensorineural hearing loss (SNHL) and auditory neuropathy (AN) ears, and providing useful information for candidates screening and outcome prediction in cochlear implantation. Methods: The frequency-specific acoustic ABR was recorded in mice. The immunohistochemical staining was performed to detect the SGNs and Schwann cells in mice cochlea. The correlations between ABR wave I metrics and SGNs, Schwann cells were investigated. Results: In SNHL and AN mice cochlea, statistically significant correlations between ABR wave I thresholds, latencies and amplitudes at 8, 16, and 32 kHz and their corresponding SGNs densities were found only in wave I amplitude at 8 kHz. While the ABR wave I metrics at all three frequencies showed strong significant correlations with their corresponding Schwann cells densities. [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.)

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.)

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.)

Conclusion: Tight fixation of the artificial trachea is important for epithelialization and tracheal stenosis. Objective: The authors have developed an artificial trachea and have used it for tracheal reconstruction. Although various studies on tracheal reconstruction have been conducted, no studies have examined the effect of artificial tracheal fixation on tracheal stenosis and regeneration. Therefore, the purpose of the present study was to evaluate the effect of artificial tracheal fixation. Study design: Preliminary animal experiment. Methods: Artificial tracheae were implanted into rabbits with partial tracheal defects. Tracheal stenosis and regeneration of the tracheal epithelium on the artificial tracheae were evaluated by endoscopic examination, scanning electron microscopic analysis, and histological examination. The artificial tracheae fixed to the tracheal defects were classified into three groups (0-point, 4-point, and 8-point) by the number of fixation points. Results: At 14 and 28 days post-implantation, the luminal surface of the implantation area was mostly covered with epithelium in all fixation groups. However, a small amount of granulation tissue was observed in the 0-point fixation group at 14 days post-implantation. Moreover, tracheal stenosis did not occur in the 8-point fixation group, but stenosis was detected in the other groups. [ABSTRACT FROM AUTHOR]

Conclusions:In this investigation, a large mammal, Rongchang pigs were used to successfully establish a research platform for cochlear implant study on the routine use of it in clinic. Objective:The aim of this study was to establish a standard method of cochlear implant in a large mammal—pig. Methods:Rongchang pigs were selected, then divided into two groups: normal-hearing group (Mitf +/+) and mutation group with hearing loss (Mitf −/−). Cochlear implants were used and ABR and EABR were recorded. The implanted electrodes were observed by X-ray and HE stains. Results:The success with cochlear implant and the best electrode position could be defined in all animals, the coiling of the cochlea reached 1.5–1.75 turns. Immediately after the operation of cochlear implants, the ABR threshold of the operated ear (right) could not be derived for each frequency at 120 dB SPL. Moreover, 7 days after surgery, the low-frequency ABR threshold of the operated ear (right) could be derived partly at 100 dB SPL, but the high-frequency ABR threshold could not be derived at 120 dB SPL. Immediately or 1 week after cochlear implants, the EABR threshold was 90 CL in the Mitf +/+ group. This was obviously lower than the 190 CL in the Mitf −/− group. [ABSTRACT FROM PUBLISHER]

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]

Conclusions:There is clear correspondence between HU and histopathological evaluation of osteitis. It is feasible to evaluate bone remodeling in rabbit models with rhinosinusitis by measuring the HU. Objective:The objective of this study was to determine whether the HUs of rabbit CRS models can be used to objectively evaluate the degree of osteitis. Methods:Sixty rabbit models were inoculated withstaphylococcus aureus. The rabbits were divided into three groups. Each group was divided into a medication administration team and a control team. The HU of the bone in each image was measured. All of the animals were executed after the CT exam. The samples for the mucous and bone changes using light microscope observation were scored. These scores and the HU measurements were compared to the actual bone remodeling over time to examine whether we could evaluate bone remodeling by measuring the HU. Results:The average HU scores in Groups A, B, and C were significantly higher than those of normal rabbits (p < .05). The mucous and bone scores increased as the experimental period lengthened (p = .042, 0.002). HU correlated with the mucous and bone scores in rabbit models with rhinosinusitis (coefficientr = .830, 0.641, 0.586,p = .000). [ABSTRACT FROM PUBLISHER]

Conclusion: Gastric type H+,K+-ATPase in the vestibular end organs may be of importance for K+ circulation and may also be related to pH regulation in vestibular end organs and endolymphatic sac. Objective: To analyze the expression of gastric-type H+,K+-ATPase in normal mouse vestibular end organs. Methods: 8 weeks old CBA/J mice were used in this study. The presence of gastric-type H+,K+-ATPase α and β in the vestibular end organs, viz. utricle, saccule, ampulla, vestibular ganglion, and endolymphatic sac, was investigated using immunohistochemistry. Results: In the vestibular end organs, H+,K+-ATPase α and β were almost identical. H+,K+-ATPase was expressed in sensory cells, the basolateral surface of dark cells, fibrocytes, in vestibular ganglion cells, and in the upper region of the endolymphatic sac epithelial cells. [ABSTRACT FROM AUTHOR]

Conclusion: Mesenchymal stem-cells are good candidates for cell-therapy of chronic tympanic membranes perforations. Objectives: To determine the effects of cell-based therapy in tympanic membrane perforations. Methods: Young C57BL/6 mice were anesthetized with intraperitoneal administration of ketamine and xylazine and randomly divided into three groups (n = 4 ears/group) that underwent bilateral sub-total pars tensa perforations of equal sizes using a sterile 27-gauge needle under a surgical microscope. Six-to-eight hours after injury, one group of mice did not receive treatment (acute perforation control), and the last two groups were treated with BM-MSCs embedded within HA scaffolds previously soaked in PBS to rinse culture media residues to avoid confounders and were euthanized 1 or 2 weeks after treatment. Results: Untreated tympanic membrane perforations developed a hyper-cellular infiltrate surrounding the injury site, while BM-MSC treated eardrums showed a reduced inflammatory response after the first week and a restoration of the trilaminar configuration 2 weeks after treatment, mimicking a normal tympanic membrane. [ABSTRACT FROM AUTHOR]

Conclusions: Human–rat geniculate ganglion (GG) have multiple origins: (1) An initial proximity (20 μm) to the endocranial foramen of the IAM, suggests neural crest induction; and (2) The influence of epibranchial placodes: the tensor tympani muscle (TTM) and the otic apical coil. Objectives: This study was undertaken to determine the comparative development of human–rat GG. Materials and methods: A light microscopic study of the GG in human material obtained from spontaneous abortions at 9, 13, 14, 17, 18, and 30 weeks, and one neonate was done. This study examined Webster rat embryos and a post-natal series. Specimens were fixed in Bouin fluid, embedded in paraffin, cut, and stained with H&E. The histomorphometric data were obtained with image analysis software. Results: The human fetus of 9 weeks presents two neuronal groups in the VII nerve: one near (20 μm) the IAM endocranial foramen, foraminal, and the other, tympanic. Neonate GG is located between the TTM and the cochlear apex (inwards). In the 16 day old rat embryo GG is placed within a canal containing the stapedial artery. In the adult rat the GG and the stapedial artery are placed within the IAM. [ABSTRACT FROM AUTHOR]

Conclusion: Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. Objectives: While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. Methods: The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. Results: While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively. [ABSTRACT FROM AUTHOR]

Conclusions:The rabbit lingual sentinel lymph node (SLN) could be long-term visualized by indirect lymphography using gadolinium-loaded polyethylenimine-entrapped gold nanoparticles (Gd-Au PENPs) as CT/MR dual-modal contrast agent. Objective:To investigate duration and intensity of rabbit lingual SLN enhancement using Gd-Au PENPs as a CT/MR dual-modal contrast agent. Methods:Twelve rabbits were randomly divided into indirect CT lymphography (CT-LG) and MR lymphography (MR-LG) groups. In each group, two rabbits received unilateral injection and four received bilateral injection of Gd-Au PENPs in the sub-mucosa of the tongue. Then the enhancement characteristics of SLN were investigated. Results:The enhanced SLNs were observed in 100% in all rabbits by indirect CT-LG and MR-LG simultaneously at 1 min after injection. Then SLN enhancement was improved rapidly and the first peaks were observed at 25 min for CT-LG and 1 h for MR-LG, respectively, then SLN enhancement decreased gradually to a minimum at 2 h for CT-LG and 3 h for MR-LG. Afterwards, the enhancement intensity increased again and second peaks were observed at 24 h for both CT-LG and MR-LG. Hereafter, the intensity dropped slowly and weak enhancement was also observed at the 40th week for CT-LG and 31st day for MR-LG. Black-stained SLNs were visualized in 100% at autopsy in all rabbits. [ABSTRACT FROM PUBLISHER]

Conclusions: The co-existence of cupulolithiasis and canalolithiasis might be a possible mechanism for the spontaneous inversion of positional nystagmus. Objective: To investigate the mechanism of spontaneous inversion of nystagmus direction without a positional change in experimental models of co-existing cupulolithiasis and canalolithiasis. Methods: Co-existing canalolithiasis and cupulolithiasis models were prepared using the bullfrog posterior semicircular canal (PSC). Ten bullfrogs were used. The ampullary nerve discharges were recorded as compound action potentials (CAPs). First, an otoconial mass was placed on the cupula to produce cupulolithiasis. Subsequently, another otoconial mass was introduced into the canal lumen to produce canalolithiasis. Decremental time constants for cupulolithiasis and incremental time constants for canalolithiasis were determined. Results: At first the CAPs increased and continued for a long time when the cupulolithiasis was generated. Subsequently the CAPs were suppressed by creating canalolithiasis. Finally, the CAPs increased again after the motion of otoconia inside the canal lumen stopped. The decremental time constant for cupulolithiasis was significantly longer than the incremental time constant for canalolithiasis. [ABSTRACT FROM AUTHOR]

Conclusion:The results showed a gradual detachment of otoconia in the utricle after a single event of head vibration, possibly explaining the frequent recurrence of BPPV attacks and persistent dizziness after trauma. Objectives:This study developed a murine model of traumatic BPPV and observed the changes in otoconia detachment over time. Methods:Six-week-old CBA mice were used in this study. Otoconia detachment was induced by vibrating the head for 2 min. Utricles of mice were harvested from different groups: before the head vibration and 1 day, 1 week, 1 month, and 3 months after vibration application. Using scanning electron microscopy and ImageJ software, the percentage of the intact area of otoconia in the utricle was calculated. Hearing thresholds were compared among the groups. Results:The mean (± SD) percentages of the intact area of otoconia in the utricle were 98.1% ± 1.7% before the vibration and 93.6% ± 1.7%, 88.9% ± 5.3%, 78.2% ± 20.9%, and 38.9% ± 24.1% at 1 day, 1 week, 1 month, and 3 months after the vibration, respectively. The percentage decreased significantly over time after the vibration (p < .001). The hearing thresholds were not different among the groups. [ABSTRACT FROM PUBLISHER]

Conclusion: The data indicate important roles for phosphodiesterase (PDE) 3, 4, 5, and related cAMP and cGMP pools in the regulation of inner ear fluid homeostasis. Thus, dysfunction of these enzymes might contribute to pathologies of the inner ear. Objective: The mechanisms underlying endolymphatic hydrops, a hallmark of inner ear dysfunction, are not known in detail; however, altered balance in cAMP and cGMP signaling systems appears to be involved. Key components of these systems are PDEs, enzymes that modulate the amplitude, duration, termination, and specificity of cAMP and cGMP signaling. Method: To evaluate the role of PDE3, 4, and 5 and associated cAMP and cGMP pools in inner ear function, the effect of cilostamide (PDE3 inhibitor), rolipram (PDE4 inhibitor), and sildenafil (PDE5 inhibitor), administrated via mini-osmotic pumps, on mouse inner ear fluid homeostasis was evaluated using 9.4T in vivo MRI in combination with intraperitoneally administered Gadolinium contrast. Also, using human saccule as a model, the expression of PDEs and related signaling molecules and targets was studied using immunohistochemistry. Results: PDE3, PDE4, as well as PDE5 inhibitors resulted in the development of endolymphatic hydrops. Furthermore, PDE3B, PDE4D, and some related signaling components were shown to be expressed in the human saccule. [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]

Conclusion:This study indicates that the lesion of hair cells in the apical turn of the cochlea can cause the change in the summating potential (SP)/Compound potential (CAP) ratio. Objectives:Electrocochleography is a valuable clinic test for diagnosis of cochlear pathologies and the ratio of SP to CAP has been used to identify Meniere’s disease. However, it remains controversial whether the increase of the SP/CAP ratio represents exclusively the endolymphatic hydrops. Method:This study measured the SP and CAP in mice that displayed outer hair cell (OHC) degeneration in the apical section of the cochlea as their age increased. Results:As compared with the mice aged 8–10 months, the 24-month old mice displayed a significant increase in the amplitude of SP at 12–16 kHz. This result suggests that the degeneration of OHCs in the apical turn leads to the increase of the + SP at the middle frequencies. In contrast, the aging mice did not have a significant change in the CAP amplitude at super-threshold levels. [ABSTRACT FROM PUBLISHER]

Objectives:This study used Tsumura Suzuki Obese Diabetes (TSOD) mice as a spontaneous type 2 diabetes model and Tsumura Suzuki Non-obesity (TSNO) mice as controls to investigate factors involved in the onset of hearing impairment. Method:Body weight, blood glucose levels, and auditory brainstem responses (ABRs) were measured. The cochleae were excised and evaluated histopathologically. Results:The TSOD mice showed significant hyperglycemia at 2–7 months and severe obesity at 5–10 months; significantly elevated ABR thresholds at 8–10 months; and the capillary lumens in the cochlea stria vascularis were narrower in the TSOD mice than in the TSNO mice. At 17 months, India ink vascular staining of the TSOD mice’s cochleae revealed decreased capillary density in the stria vascularis. The vascular area of capillaries in the stria vascularis and the vascular area were significantly smaller in TSOD mice. Histopathological analysis showed vessel wall thickening in the modiolus and narrowed capillaries in the stria vascularis, suggesting reduced blood flow to the inner ear. Conclusion:The diabetes mice model used in our study showed early age-associated hearing loss, and histopathology showed findings of vessel wall thickening in the modiolus, narrowing of capillaries in the stria vascularis, and chronically reduced blood flow in the cochlea. [ABSTRACT FROM PUBLISHER]

Conclusion:In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea. Objectives:Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide. Method:In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range = 8–32 kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status. Results:At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32 kHz. Gadodiamide application caused a significant change in the ABR threshold at 8 kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application. [ABSTRACT FROM PUBLISHER]

Conclusions: Transplantation of OECs into the cochlea may protect and increase the survival of SGCs. Objective: To investigate the protective effect of the transplantation of olfactory ensheathing cells (OECs) on injured spiral ganglion cells (SGCs) in rats. Methods: OECs were transplanted into the cochlea in rats with SGCs that were injured by kanamycin sulfate (KM). An equal volume of D-Hanks was injected into the cochlea of control rats. Auditory brainstem responses (ABRs) were recorded from the rats in both groups to monitor changes in hearing thresholds. Immunofluorescence was employed to examine the density and morphology of SGCs to assess the ototoxic condition of the cochlea. Results: There was no significant difference in the ABR threshold at each frequency between the control and experimental groups. Notably, in the experimental group, a number of Hoechst 3334-labeled nuclei were detected from the apex to the basal turn of the cochlea, demonstrating that the OECs were successfully transplanted and survived in the cochlea. In the experimental group, most of the SGCs were tightly arranged, and the nuclear membrane, chromatin, and nucleolus were all clear. The SGCs in the control group were loosely arranged, and only a few normal SGCs were observed in this group. [ABSTRACT FROM AUTHOR]

Objectives: Vestibular ganglion cells, which convey sense of motion from vestibular hair cells to the brainstem, are known to degenerate with aging and after vestibular neuritis. Thus, regeneration of vestibular ganglion cells is important to aid in the recovery of balance for associated disorders. Methods: The present study derived hNSCs from induced pluripotent stem cells (iPSCs) and transplanted these cells into mouse utricle tissues. After a 7-day co-culture period, histological and electrophysiological examinations of transplanted hNSCs were performed. Results: Injected hNSC-derived cells produced elongated axon-like structures within the utricle tissue that made contact with vestibular hair cells. A proportion of hNSC-derived cells showed spontaneous firing activities, similar to those observed in cultured mouse vestibular ganglion cells. However, hNSC-derived cells around the mouse utricle persisted as immature neurons or occasionally differentiated into putative astrocytes. Moreover, electrophysiological examination showed hNSC-derived cells around utricles did not exhibit any obvious spontaneous firing activities. Conclusions: Injected human neural stem cells (hNSCs) showed signs of morphological maturation including reconnection to denervated hair cells and partial physiological maturation, suggesting hNSC-derived cells possibly differentiated into neurons. [ABSTRACT FROM AUTHOR]

Conclusion: Nitric oxide synthase (NOS) II induction is a protective mechanism against age-related degeneration of the cochlea. Objectives: An induction of NOS II has been described in different inner ear pathologies. The objective was to examine the role of NOS II in age-related degeneration of the cochlea. Methods: The hearing ability in adult and aging NOS II knockout mice (KO) and their wildtype (WT) littermates was explored via auditory brainstem response (ABR) measurements. Inner ear morphological differences were studied with scanning electron microscopy (SEM). Immunohistochemistry was used to examine the induction of NOS II in the inner ear of aging WT mice. Expression of nitrotyrosin, a marker protein for the reactive oxygen species peroxynitrite, was compared between KO and WT mice using immunohistochemistry. Results: Adult KO mice exhibited a mild hearing impairment. WT mice showed an induction of NOS II after 6 months of age. Age-related hearing deterioration was accelerated in KO mice, which was accompanied by increased nitrotyrosin formation and outer hair cell loss. [ABSTRACT FROM AUTHOR]

Conclusion:Significant expression of macrophage migration inhibitory factor and its receptor (CD74) was observed in both the middle ear and inner ear in experimental otitis media in mice. Modulation of macrophage migration inhibitory factor and its signaling pathway might be useful in the management of inner ear inflammation due to otitis media. Objectives:Inner ear dysfunction secondary to otitis media has been reported. However, the specific mechanisms involved are not clearly understood. The aim of this study is to investigate the expression of macrophage migration inhibitory factor and CD74 in the middle ear and inner ear in lipopolysaccharide-induced otitis media. Method:BALB/c mice received a transtympanic injection of either lipopolysaccharide or phosphate-buffered saline (PBS). The mice were sacrificed 24 h after injection, and temporal bones were processed for polymerase chain reaction (PCR) analysis, histologic examination, and immunohistochemistry. Results:PCR examination revealed that the lipopolysaccharide-injected mice showed a significant up-regulation of macrophage migration inhibitory factor in both the middle ear and inner ear as compared with the PBS-injected control mice. The immunohistochemical study showed positive reactions for macrophage migration inhibitory factor and CD74 in infiltrating inflammatory cells, middle ear mucosa, and inner ear in the lipopolysaccharide-injected mice. [ABSTRACT FROM PUBLISHER]

Conclusions: The results indicate that the injury of the marginal mandibular branch improved the recovery of the buccal branch in a rat model. Objective: The aim of this study was to investigate whether the injury or intactness of the marginal mandibular branch affects the regeneration of the facial nerve buccal branch in a rat model. Methods: This experiment was conducted on 30 adult rats, which were randomly and equally divided into two groups. The buccal branch of the facial nerve was transected and reconstructed, with the marginal mandibular branch damaged (group A) or intact (group B). The vibrissae movement of rats was assessed since the 4th week after operation. At the 8th and 12th week, compound muscle action potentials (CMAPs) and morphological changes of injured buccal branches were evaluated. Results: After the operation, vibrissae movement of rats was eliminated in group A, but it was similar to the health side in group B. CMAPs were recorded from regenerated buccal branches in group A since the 8th week, but no CMAPs could be recorded in group B at each time point. Additionally, the diameter of nerve fibers, the thickness of myelin sheath, and the density of regenerated fibers in group A were significantly larger than those in group B (p < 0.05). [ABSTRACT FROM PUBLISHER]

Conclusion: The increased AQP5 expression associated with ageing in glands, which mainly secreted a serous solution, suggests a compensation for the decreased amount of saliva secretion associated with age progression.Objective: To investigate the change in aquaporin-1 (AQP1) and aquaporin-5 (AQP5) expression in the salivary glands in young and elder mice.Materials and method: Twelve female mice from the Balb/C genus (30–50 g) were used. The mice were separated into two groups: Group I had 2-month-old mice and Group II had 18-month-old mice. Salivary glands (glandula parotidea, glandula sublungualis, glandula submaxillaris) were excised and examined immunohistochemically and histopathologically. AQP1 and AQP5 expression of young and elder mice was evaluated using the H-score. Ap-value less than 0.05 was considered statistically significant.Results: Upon histopathological examination, the acini of glands were found to be atrophic in elder mice. The number and diameter of intercalated ducts were increased. Indeed, the amount of adipose tissue in the gland was increased. Upon immunohistochemical examination, both AQP1 and AQP5 levels in sublingual glands of elder mice were increased (p < 0.01 andp < 0.001, respectively). However, only AQP5 levels were increased in the parotid gland of elder mice (p < 0.01). [ABSTRACT FROM PUBLISHER]

Conclusion: Down-regulation of ECD may associate with infiltrative tumor growth and result in poor prognosis. However, ECD expression is not significantly associated with tumor metastasis.Aim: To investigate the prognostic role of E-cadherin (ECD) expression in laryngeal cancer.Methods: In a clinical study, a total of 79 laryngeal cancer patients who received surgery were included in this study. The expression of ECD in laryngeal cancer tissue was detected by immumohistochemical staining. In anin vitrostudy, ECD up-regulated cells (Ad-ECD) and ECD down-regulated cells (sh-ECD) were cultured, along with interference by siRNA. Cell apoptosis was detected by flow cytometry. In anin vivostudy, nude mice were injected with Ad-ECD, sh-ECD, and Hep-2 cells. The ECD expression and tumor metastasis in the brain, liver, and lung tissues were detected.Results: Clinical data showed that expression of ECD was statistically correlated with survival rate (p < 0.05), but not with other clinical characteristics, such as age, gender, lymphatic metastasis, and TNM staging. ECD was down-regulated in sh-ECD cells and the down-regulation significantly reduced apoptosis of Hep-2 cells. Tumor growth was significantly inhibited in the Ad-ECD group. Except the tumor tissue, no positive ECD expression or significant tumor cells were found in the brain, liver, and lung tissues. [ABSTRACT FROM PUBLISHER]

Conclusion SM-induced dose- and location-dependent cochlear hair cell death in vitro. AIF might be translocated from mitochondria to nucleus and cytoplasm within SM-treated hair cells. The translocation of AIF might be modulated by PARP-1. Objective Streptomycin (SM), one of the widely used aminoglycoside nowadays, is still causing significant permanent sensorineural hearing loss owing to sensory hair cell death. This study was designed to investigate the role of apoptosis-inducing factor (AIF), an important mitochondrial cell death regulator, in SM ototoxicity within neonatal rat cochleae and HEI-OC1 cells. Methods The viability of HEI-OC1 cells was quantified by MTT assay. AIF, PARP-1, and myosin VIIa distributions were achieved by immunofluorescence. mRNA and protein expression of AIF and PARP-1 were examined by q-PCR and Western-blot. Results The hair cell loss was concomitant with the SM concentration variation, and aggravated from apical to basal turn. AIF was detected in nuclear region and AIF mRNA was up-regulated after SM incubation. Besides, AIF protein expression in mitochondria was decreased, whereas in cytosol it was increased. PARP-1 mRNA and protein were also up-regulated. 3-AB could attenuate the cell death and reverse the changes of AIF distribution by blocking PARP-1. [ABSTRACT FROM AUTHOR]

ConclusionC/GP hydrogel was demonstrated to be an ideal drug delivery vehicle and scaffold in the vein conduit. Combined use autologous vein and NGF continuously delivered by C/GP-NGF hydrogel can improve the recovery of facial nerve defects.ObjectiveThis study investigated the effects of chitosan-β-glycerophosphate-nerve growth factor (C/GP-NGF) hydrogel combined with autologous vein conduit on the recovery of damaged facial nerve in a rat model.MethodsA 5 mm gap in the buccal branch of a rat facial nerve was reconstructed with an autologous vein. Next, C/GP-NGF hydrogel was injected into the vein conduit. In negative control groups, NGF solution or phosphate-buffered saline (PBS) was injected into the vein conduits, respectively. Autologous implantation was used as a positive control group. Vibrissae movement, electrophysiological assessment, and morphological analysis of regenerated nerves were performed to assess nerve regeneration.ResultsNGF continuously released from C/GP-NGF hydrogelin vitro. The recovery rate of vibrissae movement and the compound muscle action potentials of regenerated facial nerve in the C/GP-NGF group were similar to those in the Auto group, and significantly better than those in the NGF group. Furthermore, larger regenerated axons and thicker myelin sheaths were obtained in the C/GP-NGF group than those in the NGF group. [ABSTRACT FROM PUBLISHER]

Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors. [ABSTRACT FROM AUTHOR]

ConclusionModerate hearing loss in young mice caused decreases in cognition associated with spatial working and recognition memories in 6 months. These results provide evidence for a causal relationship between hearing loss and cognitive impairment.ObjectivesHypothesized mechanisms to connect sensory and cognitive functions include the sensory-deprivation, information-degradation, and common-cause hypotheses. This study intended to investigate the effect of hearing loss on cognitive function, as estimated by radial arm maze (RAM) and novel object recognition (NOR) tasks in mice through age- and hearing-matched longitudinal work during a 6-month period.MethodsTwenty-four male C57BL/6 mice aged 1 month with normal ABR thresholds were used. Twelve mice in the hearing loss (HL) group were exposed to white noise at 110 dB SPL for 60 min every day for 20 days. At post-noise 6 months, all mice underwent RAM and one-trial NOR test. RAM performance measures and NOR discrimination index were compared between two groups.ResultsAt 6 months after noise exposure, all mice in the experimental group had moderate hearing loss. Most of the RAM performances improved gradually within each group across five trials, probably due to learning effect. The HL group showed lower performance scores than the control group in several trial points in the RAM task. The contact time with the novel object was shorter in the HL group than in the control group. [ABSTRACT FROM PUBLISHER]

ConclusionsA cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs.ObjectiveInner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT.MethodsOC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. Control group: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 μg/mL); (4) EIT + L-NAC + Mannitol + Dex. After EIT was caused in anin-vitromodel of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4.ResultsThere was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri-therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cellsin vitro. Their combination provided close to 96% protection, demonstrating an additive effect. [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]

Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation. [ABSTRACT FROM AUTHOR]

ConclusionWith age, in a mouse model, degenerative changes to the capillaries of the stria vascularis are observed. These range from a narrowing of vessel lumen to complete degeneration of strial vessels. Other vascular beds in the cochlea are relatively unchanged with age. Strial capillaries at the cochlear base are significantly more affected than those in mid-apical turns. ObjectivesPrevious work suggests that age-related hearing loss is associated with degenerative changes to cochlear vasculature; the term strial presbyacusis is often cited. This study reports on vascular changes observed in a murine model of presbyacusis, analyzed using corrosion cast techniques. MethodsA novel corrosion cast technique was developed to compare cochlear vasculature in control mice (non-presbycusic, CD1) and old (> 6 months) C57BL/6 animals. ABR measures indicated a significant age-related threshold elevation in the C57BL/6 mice. Cochlear vascular casts were imaged using scanning electron microscopy, and vessel degeneration was quantified by measuring capillary diameters. ResultsCorrosion casts of cochlear vasculature in 6–12 month old C57BL/6 mice reveal significant degeneration of stria vascularis. Other capillary beds (spiral ligament and the spiral limbus) appear unchanged. Comparison of strial capillary diameters reveals significantly more damage in basal/lower-turn regions compared with the cochlear mid-turn. [ABSTRACT FROM PUBLISHER]