Secondary Degeneration of Auditory Neurons after Topical Aminoglycoside Administration in a Gerbil Model

Hair cells in the cochlea can be damaged by various causes. Damaged hair cells can lead to additional destruction of parts of the auditory afferent pathway sequentially, which is called secondary degeneration. Recently, researches regarding cochlear implants have been actively carried out for clinical purposes; secondary degeneration in animals is a much more practical model for identifying the prognosis of cochlear implants. However, an appropriate model for this research is not established yet. Thus, we developed a secondary degeneration model using an ototoxic drug. 35 gerbils were separated into four different groups and kanamycin was applied via various approaches. ABR was measured several times after drug administration. SGCs were also counted to identify any secondary degeneration. The results showed that outer and inner HCs were damaged in all kanamycin-treated groups. Twelve weeks after kanamycin treatment, the round window membrane injection group showed severe subject differences in hair cells and SGC damage, whereas the gelfoam group showed consistent and severe damage in hair cells and SGCs. In this study, we successfully induced secondary degeneration in hair cells in a gerbil model. This model can be used for various purposes in the hearing research area either for treatment or for preservation.

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Histopathological and audiological effects of mechanical trauma associated with the placement of an intracochlear electrode, and the benefit of corticosteroid infusion: prospective animal study

The Journal of Laryngology & Otology ◽

10.1017/s002221511400156x ◽

2014 ◽

Vol 128 (8) ◽

pp. 702-708 ◽

Cited By ~ 5

Author(s):

G Malkoc ◽

A Dalgic ◽

M Koc ◽

T Kandogan ◽

S Korkmaz ◽

...

Keyword(s):

Hearing Loss ◽

Topical Corticosteroid ◽

Animal Study ◽

Hair Cells ◽

Normal Saline ◽

Round Window ◽

Osmotic Pump ◽

Mechanical Trauma ◽

Round Window Membrane ◽

Scala Tympani

AbstractObjective:This study aimed to present the histopathological and audiological effects of mechanical trauma associated with the placement of a model electrode in the scala tympani in rats, and the effects of continuous topical corticosteroid application.Method:The study comprised three groups of rats. The round window membrane was perforated in all three groups and a model electrode was inserted in the round window. Group one received no further treatments. Groups two and three also had an intrathecal microcatheter compatible with a mini-osmotic pump inserted; in group two this was used to release normal saline and in group three the pump released 400 µg/ml dexamethasone.Results:Dexamethasone infusion given after implantation of the intracochlear model electrode was more effective for preventing hearing loss than the administration of just one dose of dexamethasone.Conclusion:The findings suggest that continuous dexamethasone infusion is beneficial for preventing the loss of hair cells and neurons associated with early and late periods of intracochlear electrode trauma.

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Brain-derived neurotrophic factor gene therapy prevents spiral ganglion degeneration after hair cell loss

Otolaryngology ◽

10.1016/s0194-5998(98)70194-9 ◽

1998 ◽

Vol 119 (1) ◽

pp. 7-13 ◽

Cited By ~ 127

Author(s):

Hinrich Staecker ◽

Ramin Gabaizadeh ◽

Howard Federoff ◽

Thomas R. Van De Water

Keyword(s):

Hair Cells ◽

Neurotrophic Factor ◽

Spiral Ganglion ◽

Brain Derived Neurotrophic Factor ◽

In Vivo Studies ◽

Auditory Neurons ◽

Secondary Degeneration ◽

Auditory Hair Cells ◽

Neurotrophin 3

Destruction of auditory hair cells results in the secondary degeneration of auditory neurons. This is because of the loss of neurotrophic factor support from the auditory hair cells, namely neurotrophin 3, which is normally produced by the inner hair cells. Both in vitro and in vivo studies have shown that delivery of either neurotrophin 3 or brain-derived neurotrophic factor to these neurons can replace the trophic support supplied by the hair cells and prevent their degeneration. To prevent the degeneration of auditory neurons that occurs after neomycin destruction of the auditory hair cells we used a replication defective herpes simplex-1 vector (HSVbdnflac) to transfect the gene for brain-derived neurotrophic factor into the damaged spiral ganglion. Four weeks after the HSVbdnflac therapy we were able to detect stable functional production of brain-derived neurotrophic factor that supported the survival of auditory neurons and prevented the loss of these neurons because of trophic factor deprivation-induced apoptosis. (Otolaryngol Head Neck Surg 1998;119:7–13.)

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Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.710159 ◽

2021 ◽

Vol 9 ◽

Author(s):

Silvia T. Erni ◽

John C. Gill ◽

Carlotta Palaferri ◽

Gabriella Fernandes ◽

Michelle Buri ◽

...

Keyword(s):

Hair Cell ◽

Notch Signaling ◽

Hair Cells ◽

Round Window ◽

Notch Pathway ◽

Outer Hair Cells ◽

Round Window Membrane ◽

Sensory Cells ◽

Supporting Cells

Sensorineural hearing loss is prevalent within society affecting the quality of life of 460 million worldwide. In the majority of cases, this is due to insult or degeneration of mechanosensory hair cells in the cochlea. In adult mammals, hair cell loss is irreversible as sensory cells are not replaced spontaneously. Genetic inhibition of Notch signaling had been shown to induce hair cell formation by transdifferentiation of supporting cells in young postnatal rodents and provided an impetus for targeting Notch pathway with small molecule inhibitors for hearing restoration. Here, the oto-regenerative potential of different γ-secretase inhibitors (GSIs) was evaluated in complementary assay models, including cell lines, organotypic cultures of the organ of Corti and cochlear organoids to characterize two novel GSIs (CPD3 and CPD8). GSI-treatment induced hair cell gene expression in all these models and was effective in increasing hair cell numbers, in particular outer hair cells, both in baseline conditions and in response to ototoxic damage. Hair cells were generated from transdifferentiation of supporting cells. Similar findings were obtained in cochlear organoid cultures, used for the first time to probe regeneration following sisomicin-induced damage. Finally, effective absorption of a novel GSI through the round window membrane and hair cell induction was attained in a whole cochlea culture model and in vivo pharmacokinetic comparisons of transtympanic delivery of GSIs and different vehicle formulations were successfully conducted in guinea pigs. This preclinical evaluation of targeting Notch signaling with novel GSIs illustrates methods of characterization for hearing restoration molecules, enabling translation to more complex animal studies and clinical research.

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Effect of Experimentally Induced Otitis Media on Cochlear Implants

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348948709600207 ◽

1987 ◽

Vol 96 (2) ◽

pp. 174-177 ◽

Cited By ~ 20

Author(s):

Burkhard K-H. Franz ◽

Graeme M. Clark ◽

David M. Bloom

Keyword(s):

Horseradish Peroxidase ◽

Cochlear Implants ◽

Round Window ◽

Round Window Membrane ◽

Group A Streptococci ◽

Scala Tympani ◽

Tracer Studies ◽

Entry Points ◽

Group A ◽

Round Window Niche

Cat cochleas implanted with scala tympani prostheses were investigated histologically after inoculating the bullae with a suspension of group a streptococci. The prosthesis was passed through the round window membrane in one ear. In the other the prosthesis bypassed the round window via an opening anteroinferior to the round window niche. Before death, horseradish peroxidase was administered as a tracer for possible pathways of infection. Results showed that group a streptococci were pathogenic to the cat and caused inflammation in the bulla. The unimplanted round window membrane and the seals around the electrode entry points prevented infection from entering the cochlea. The seals around electrodes inserted either through the round window membrane or an opening drilled anteroinferior to the niche were equally effective. The horseradish peroxidase tracer studies showed, however, that a gap existed between the electrode and membranous seal, and this could be a potentially vulnerable site under certain conditions. Drilling an anteroinferior opening into the cochlea resulted in bony sequestra entering the cochlea. This can be avoided by blue-lining the opening and removing bone with picks before making an opening through the endosteum.

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Further studies on the ultrastructure of the cochlea

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159746 ◽

1990 ◽

Vol 48 (3) ◽

pp. 440-441

Author(s):

Zhixian Wang ◽

Pinjin Zhu ◽

Jianhe Sun ◽

Xuezheng Song

Keyword(s):

Hair Cells ◽

Military Medicine ◽

Outer Hair Cells ◽

Apical Surface ◽

Epithelial Surface ◽

Hearing Research ◽

New Findings ◽

Fine Structures ◽

Temporal Bones ◽

Accurate Observation

Hearing research is important not only for clinical, professional and military medicine, but also for toxicology, gerontology and genetics. Ultrastructure of the cochlea attracts much attention of electron microscopists, (1―3) but the research lags far behind that of the other parts of the organnism. On the basis of careful microdissection, technical improvment and accurate observation, we have got some new findings which have not been reported in the literature.We collected four cochleas from human corpses. Temporal bones dissected 1 h after death and cochleas perfused with fixatives 4 h after death were good enough in terms of preservation of fine structures. SEM:The apical surface of OHCs (Outer hair cells) and DTs (Deiters cells) is narrower than that of IPs (Inner pillar cells). The mosaic configuration of the reticular membrane is not typical. The stereocilia of IHCs (Inner hair cells) are not uniform and some kinocilia could be seen on the OHCs in adults. The epithelial surface of RM (Reissner’s membrane) is not smooth and no mesh could be seen on the mesothelial surface of RM. TEM.

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The Effects of Round Window Membrane Injury and the Use of a Model Electrode Application on Hearing in Rats

Ear Nose & Throat Journal ◽

10.1177/0145561321990188 ◽

2021 ◽

pp. 014556132199018

Author(s):

Murat Koc ◽

Abdullah Dalgic ◽

Mehmet Ziya Ozuer

Keyword(s):

Hearing Loss ◽

Cochlear Implant ◽

Round Window ◽

Mechanical Trauma ◽

Round Window Membrane ◽

Albino Rats ◽

Topical Steroids ◽

Distortion Product ◽

Significant Difference ◽

Group 3

Objective: To investigate the effects of the mechanical trauma to the round window, a model electrode inserted into the scala tympani on the cochlear reserve, and the efficacy of topical steroids in preventing hearing loss. Materials and Methods: 21 male Wistar Albino rats were equally categorized into three groups. In all groups an initial mechanical injury to round window was created. Only subsequent dexamethasone injection was administrated into the cochlea in the subjects of group 2 while a multichannel cochlear implant guide inserted into the cochlea prior to dexamethasone administration for group 3. Distortion product otoacoustic emissions (DPOAEs) were obtained prior to and immediately after the surgical injury, eventually on postoperative seventh day (d 7). Mean signal/noise ratios (S/Ns) obtained at 2000, 3000, and 4000 Hz were calculated. Data sets were compared with non-parametric statistical tests. Results: The early intraoperative mean S/Ns were significantly less than preoperative measurements for group 1 and 2; however, preoperative and postoperative d 7 average S/Ns did not differ. There was statistically significant difference between preoperative, intraoperative and postoperative d 7 average S/Ns for group 3. Conclusion: We observed that hearing was restored approximately to the preoperative levels following early postoperative repair. However, an electrode insertion into the cochlea via round window subsequent to mechanical trauma seems to cause a progressive hearing loss. Therefore, a special care must be taken to avoid the injury to the round window membrane in the course of the placement of a cochlear implant electrode and surgery for the chronic otitis media.

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Cochlear Implantation Following Explorative Tympanotomy in Patients With Sudden Sensorineural Hearing Loss: Surgical Features and Audiological Outcomes

Ear Nose & Throat Journal ◽

10.1177/01455613211009141 ◽

2021 ◽

pp. 014556132110091

Author(s):

Robin Rupp ◽

Joachim Hornung ◽

Matthias Balk ◽

Matti Sievert ◽

Sarina Müller ◽

...

Keyword(s):

Hearing Loss ◽

Connective Tissue ◽

Sensorineural Hearing Loss ◽

Cochlear Implantation ◽

Round Window ◽

Sudden Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Round Window Membrane ◽

Hearing Results ◽

Round Window Niche

Objective: To investigate the anatomical status of the round window niche and hearing outcome of cochlear implantation (CI) after explorative tympanotomy (ExT) with sealing of the round window membrane in patients with sudden sensorineural hearing loss at a tertiary referral medical center. Methods: Between January 1, 2007, and July 30, 2020, 1602 patients underwent CI at our department. Out of these, all patients previously treated by ExT with sealing of the round window membrane because of unilateral sudden hearing loss were included in the study. A retrospective chart review was conducted concerning method of round window membrane sealing, intraoperative findings during CI, postoperative imaging, and hearing results. Results: Twenty one patients (9 females; 8 right ears; 54.3 years [± 12.9 years]) underwent ExT with sealing of the round window membrane with subsequent CI after 26.6 months (± 32.9 mo) on average. During CI, in 76% of cases (n = 16), the round window niche was blocked by connective tissue due to the previous intervention but could be removed completely in all cases. The connective tissue itself and its removal had no detrimental effects on the round window membrane. Postoperative computed tomography scan showed no electrode dislocation. Mean postoperative word recognition score after 3 months was 57.4% (± 17.2%) and improved significantly to 73.1% (± 16.4%, P = .005) after 2 years. Conclusion: Performing CI after preceding ExT, connective tissue has to be expected blocking the round window niche. Remaining tissue can be removed safely and does not alter the round window membrane allowing for a proper electrode insertion. Short- and long-term hearing results are satisfactory. Consequently, ExT with sealing of the round window membrane in patients with sudden sensorineural hearing loss does not impede subsequent CI that can still be performed safely.

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