Direct drug application to the round window: A comparative study of ototoxicity in rats

2009 ◽  
Vol 141 (5) ◽  
pp. 584-590 ◽  
Author(s):  
Silvia Murillo-Cuesta ◽  
Fernando García-Alcántara ◽  
Elena Vacas ◽  
Jon Alexander Sistiaga ◽  
Guadalupe Camarero ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Cell Damage ◽  
Round Window ◽  
Drug Application ◽  
Local Drug Delivery ◽  
Saline Control ◽  
Round Window Membrane ◽  
Cochlear Function ◽  
Profound Hearing Loss ◽  
Brainstem Response

Objective: To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window. Study Design: Basic, randomized, nonblind experimental study. Setting: Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies. Subjects and Methods: Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed. Results: Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations. Conclusion: Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.

S228 – Direct Round Window Drug Application and Ototoxicity in Rats

2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P151-P151
Author(s):  
Teresa Rivera ◽  
Fernando García Alcantara ◽  
Jon Alexander Sistiaga Suarez ◽  
Murillo-Cuesta Silvia ◽  
Vacas Elena ◽  
...  
Keyword(s):  
Round Window ◽  
Drug Application ◽  
Tone Burst ◽  
Auditory Brainstem ◽  
Round Window Membrane ◽  
Control Group ◽  
Cochlear Function ◽  
Before And After ◽  
Male Wistar Rats ◽  
Brainstem Response

Objectives 1) Manage to introduce ototoxic drugs, such as kanamycin and furosemide, directly on the round window in rats. 2) Use a purified gelatine sponge as a proper delivery vehicle. The purpose of the study is to assess the validity of this method to provoke local ototoxicity. Methods We carried out an experimental design with 3 groups of 6 male Wistar rats. The bulla and round window membrane were exposed using a ventral approach. In the first control group we only made a hole in the tympanic bulla. Second control group was treated with saline solution. The problem group was treated with 20 mg/kg of kanamycin and 5 mg/Kg of furosemide-soaked gelatine sponge directly upon the round window membrane. Cochlear function was assessed through tone burst auditory brainstem response (ABR) threshold (dB) and peak latency (ms) measurements. Anova with bonferroni correction was used (p level=0.05). Results All animals treated with kanamycin and furosemide exhibited significant increase in ABR threshold (x = 51.25 dB; SD = 6.29; p = 0,001) in contrast to the other groups, whose ABR thresholds did not show significant differences before and after treatment(x=31,50 dB; SD=5.53); and not significant increase in peak latencies I (x = 0.22 ms; SD = 0.12), II (x = 0.22 ms; SD = 0.20) and IV (x = 0.21 ms; SD = 0.18). Conclusions The ventral approach and placement of kanamycin and furosemide-soaked gelatine sponge directly upon the round window membrane represents a reliable method for ototoxicity in rats.

scholarly journals A gyógyszeres kezelésre nem javuló hirtelen halláscsökkenés lépcsőzetes sebészi terápiája

2021 ◽  
Vol 162 (51) ◽  
pp. 2055-2060
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Hearing Aids ◽  
Cochlear Implantation ◽  
Early Stage ◽  
Round Window ◽  
Complete Recovery ◽  
Round Window Membrane ◽  
Systemic Steroid ◽  
Profound Hearing Loss

Összefoglaló. A hirtelen halláscsökkenés patofiziológiája még nagyrészt tisztázatlan, így oki terápia nem lehetséges. Az elsődleges kezelést a helyileg vagy szisztémásan adott kortikoszteroid jelenti, egységes protokoll azonban nem áll rendelkezésre. Nagy vagy súlyos fokú hirtelen halláscsökkenés esetén kóroki tényezőként felmerül a perilymphafistula lehetősége még azoknál a betegeknél is, akiknél nem szerepel trauma az anamnézisben. A kórkép műtéti kezelése a dobüreg feltárását követően a belső fül ablakainak obliterálása. Amennyiben ez a megoldás nem eredményez megfelelő hallásjavulást, hagyományos vagy implantálható hallókészülékek alkalmazása javasolt. A közleményben részletezett esetünkben teljes siketséggel járó, jobb oldali hirtelen halláscsökkenés alakult ki, melynek hátterében egyértelmű okot azonosítani nem sikerült. Az eredménytelen kombinált, intratympanalis és szisztémás szteroidkezelést követően exploratív tympanotomiát végeztünk, melynek során a belső fül ablakait obliteráltuk. Hallásjavulást ezt követően sem sikerült kimutatni, így cochlearis implantáció elvégzése mellett döntöttünk. Az implantációt a kerek ablakon keresztül végeztük, mely alapján kijelenthetjük, hogy az előzetes kerekablak-obliteráció nem zárja ki a későbbi cochlearis implantációt. Orv Hetil. 2021; 162(51): 2055–2060. Summary. The pathophysiology of sudden sensorineural hearing loss is mainly unknown, therefore no causative treatment exists. Systemic and local administration of corticosteroids serves as first line therapy although protocols vary. In cases of severe or profound hearing loss with no improvement for medical therapy, perilymphatic fistulae can be assumed even without any history of trauma. Therefore, inner ear window obliteration as a primary surgical option in the early stage can be considered. For patients without complete recovery, conventional hearing aids or implantable hearing devices can be offered. In our case report, we present a patient with right sided idiopathic sudden deafness. After failure of conservative combined intratympanic and systemic steroid therapy, explorative tympanotomy and obliteration of the inner ear windows were performed. As no hearing improvement was witnessed, successful cochlear implantation via round window insertion was performed. Our case justifies that obliterating the round window membrane does not rule out further successful cochlear implantation. Orv Hetil. 2021; 162(51): 2055–2060.

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

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.

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

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.

scholarly journals Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3626
Author(s):  
Yi-Chun Lin ◽  
Yuan-Yung Lin ◽  
Hsin-Chien Chen ◽  
Chao-Yin Kuo ◽  
Ai-Ho Liao ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Inner Ear ◽  
Outer Hair Cells ◽  
Round Window Membrane ◽  
Insulin Like Growth Factor ◽  
Noise Induced Hearing Loss ◽  
Ear Diseases ◽  
Brainstem Response ◽  
Ultrasound Microbubbles

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

scholarly journals The Physiologic and Psychophysical Consequences of Severe-to-Profound Hearing Loss

2018 ◽  
Vol 39 (04) ◽  
pp. 349-363 ◽  
Author(s):  
Eric Hoover ◽  
Pamela Souza
Keyword(s):  
Hearing Loss ◽  
Speech Recognition ◽  
Treatment Options ◽  
Sufficient Information ◽  
Noisy Environments ◽  
Cochlear Function ◽  
Profound Hearing Loss ◽  
Sound Perception ◽  
Severe Hearing Loss ◽  
Tuning Curves

AbstractSubstantial loss of cochlear function is required to elevate pure-tone thresholds to the severe hearing loss range; yet, individuals with severe or profound hearing loss continue to rely on hearing for communication. Despite the impairment, sufficient information is encoded at the periphery to make acoustic hearing a viable option. However, the probability of significant cochlear and/or neural damage associated with the loss has consequences for sound perception and speech recognition. These consequences include degraded frequency selectivity, which can be assessed with tests including psychoacoustic tuning curves and broadband rippled stimuli. Because speech recognition depends on the ability to resolve frequency detail, a listener with severe hearing loss is likely to have impaired communication in both quiet and noisy environments. However, the extent of the impairment varies widely among individuals. A better understanding of the fundamental abilities of listeners with severe and profound hearing loss and the consequences of those abilities for communication can support directed treatment options in this population.

scholarly journals Preoperative Evaluation and Surgical Outcome of Cochlear Implantation in NIENT

2020 ◽  
Vol 26 (2) ◽  
pp. 128-135
Author(s):  
Md Zakaria Sarker ◽  
Muhammad Rafiqul Islam ◽  
Utpal Kumar Dutta ◽  
Debabrota Roy ◽  
AHM Ferdows Nur ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Facial Nerve ◽  
Psychosocial Development ◽  
Cochlear Implantation ◽  
Preoperative Evaluation ◽  
Round Window ◽  
Round Window Membrane ◽  
Safe Procedure ◽  
Female Ratio ◽  
Facial Recess

Background: Sensory neural hearing loss (SNHL) is the most common congenital sensory deficit, with an incidence of one to three per 1000 live births. Acoustic deprivation during the first 3 years of life can hinder speech and language acquisition with significant negative consequences on a child’s educational and psychosocial development. The gold standard intervention for permanent severe to profound hearing loss is cochlear implantation. Cochlear implant (CI); is a semi implantable electronic device that bypass the cochlea. Objectives: An observational study was carried out on 40 cases of pre-lingual deaf to find out the causes of pre-lingual deaf, to evaluate the preoperative procedures to set ideal criteria for pre -lingual cochlear implantation and to evaluate surgical procedure and outcome of cochlear implantations. Methods: Evaluation of the candidates included patient medical history, general health checkup, ENT examination, audiometric evaluation, CT and MRI scans, psychological profile of the candidate. A limited cortical mastoidectomy was performed. The facial recess was opened using the fossa of incudis as an initial landmark. The round window niche was visualized through the facial recess about 2 mm inferior to the stapes. A cochleostomy created by drilling over the basal turn of the cochlea anterior and inferior to the annulus of the round window membrane. The electrode array was then carefully inserted through the fenestra into the scala tympani of the cochlea. Electrophysiological testing (Neural Response Telemetry: NRT) was performed to verify the correct placement of active electrodes. Resulst: Among them 22 (55%) were male and 18 (45%) were female. Male female ratio was 1.2:1. Age distribution at implantation was 3.3±1.054(SD). Average hearing loss was 96.4±5.3(SD) dB and in aided audiogram was 63.7±4.6(SD) dB. Overall complications occurred in 10 (25%) cases. Transient facial nerve paresis in 2 (5%), injury of tympanic membrane in 1(2.5%), seroma 4(10%) and delayed otitis media in 1(2.5%) were observed. Major postoperative complications occurred in 2 cases including facial nerve palsy in 1(2.5%) case and spontaneous device failure in 1(2.5%) case. Conclusion: The result of this survey was find out the risk factor of congenital hearing loss. With a thorough preoperative evaluation, we can select proper candidates for CI which is a reliable and safe procedure with a low percentage of severe complication. Bangladesh J Otorhinolaryngol; October 2020; 26(2): 128-135

scholarly journals Efficiency of a Dexamethasone Nanosuspension as an Intratympanic Injection for Acute Hearing Loss

2021 ◽  
Author(s):  
So-Young Jung ◽  
Zion Kang ◽  
Soonmin Kwon ◽  
Juhye Lee ◽  
Subin Kim ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Inner Ear ◽  
Round Window ◽  
Round Window Membrane ◽  
In Vivo Test ◽  
Drug Concentrations ◽  
Intratympanic Injection ◽  
Acute Hearing Loss

Abstract Background: Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug for intratympanic injection in acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of dexamethasone nanosuspensions as intratympanic injection because the lipophilicity of drugs can affect their permeation of the round window membrane, an important pathway from the middle ear to the cochlea.Results: Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanocrystals in the three nanosuspensions were between approximately 250 and 350 nm in size. In order to compare the efficiency of Dex-SP and a dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography–mass spectrometry. The dexamethasone nanosuspensions showed significantly higher drug concentrations in perilymph and cochlear tissue than Dex-SP at 6 h; interestingly, animals treated with a nanosuspension showed a 26-fold higher dexamethasone concentration in the cochlear tissue than the Dex-SP group. In addition, the dexamethasone nanosuspension achieved better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, it showed a significantly better hearing protective effect than Dex-SP against ototoxic drugs. In safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL in an in vivo test.Conclusions: A nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection. In addition, it can be applied in studies on the delivery of various hydrophobic antioxidants to treat acute hearing loss.

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