Permanent and transient effects of locally delivered n-acetyl cysteine in a guinea pig model of cochlear implantation

Eastwood, Hayden; Pinder, Darren; James, David; Chang, Andrew; Galloway, Stuart; Richardson, Rachael T.; O’Leary, Stephen

doi:10.1016/j.heares.2009.08.010

Cited by 52 publications

(39 citation statements)

References 54 publications

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“…The experimental groups have been described in detail previously (Table 1) (Connolly et al, 2010;Eastwood et al, 2010;James et al, 2008;Maini et al, 2009;Souter et al, 2012). In the topical dexamethasone study (James et al, 2008), a carboxylmethylcellulose hyaluronic acid polymeric pledget (SeprapackÔ, Genzyme Corporation) was loaded with 5 ml of either 2% dexamethasone phosphate or saline and placed on the round window membrane for 30 min prior to cochlear implantation.…”

Section: Experimental Groupsmentioning

confidence: 99%

Relations between cochlear histopathology and hearing loss in experimental cochlear implantation

et al. 2013

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This study reviews the cochlear histology from four hearing preservation cochlear implantation experiments conducted on 73 guinea pigs from our institution, and relates histopathological findings to residual hearing. All guinea pigs had normal hearing prior to surgery and underwent cochlear implantation via a cochleostomy with a silastic-platinum dummy electrode. Pure tone auditory brainstem response (ABR) thresholds from 2 to 32 kHz were recorded prior to surgery, and at one and four weeks postoperatively. The cochleae were then fixed in paraformaldehyde, decalcified, paraffin embedded, and mid-modiolar sections were prepared. The treatment groups were as follows: 1) Systemic dexamethasone, 0.2 mg/kg administered 1 h before implantation, 2) Local dexamethasone, 2% applied topically to the round window for 30 min prior to cochlear implantation, 3) Local n-acetyl cysteine, 200 μg applied topically to the round window for 30 min prior to implantation, 4) inoculation to keyhole-limpet hemocyanin (KLH) prior to implantation, and 5) untreated controls. There was a significant correlation between the extent of the tissue reaction in the cochlea and the presence of foreign body giant cells (FBGCs), new bone formation and injury to the osseous spiral lamina (OSL). The extent of the tissue response, as a percentage of the area of the scala tympani, limited the best hearing that was observed four weeks after cochlear implantation. Poorer hearing at four weeks correlated with a more extensive tissue response, lower outer hair cell (OHC) counts and OSL injury in the basal turn. Progressive hearing loss was also correlated with the extent of tissue response. Hearing at 2 kHz, which corresponds to the region of the second cochlear turn, did not correspond with loco-regional inner hair cell (IHC), OHC or SGC counts. We conclude that cochlear injury is associated with poorer hearing early after implantation. The tissue response is related to indices of cochlear inflammation and injury. An extensive tissue response limits hearing at four weeks, and correlates with progressive hearing loss. These latter effects may be due to inflammation, but would also be consistent with interference of cochlear mechanics.

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Section: Experimental Groupsmentioning

confidence: 99%

Relations between cochlear histopathology and hearing loss in experimental cochlear implantation

et al. 2013

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“…19,30 Although it has only been postulated that free radical formation causes cochlear cell damage following electrode insertion, this hypothesis has strong support from the results of experiments that demonstrate that treatment with antioxidant precursor N-acetyl cysteine prevents hearing loss in a guinea pig model of cochlear implantation. 31 Delayed Hearing Loss. Besides the early events following cochlear implantation, fibrotic proliferation of tissues within the cochlea may occur and provoke the progressive delayed loss of residual hearing.…”

Section: Molecular Pathways Involved In Hearing Loss After Cochlear Imentioning

confidence: 99%

Molecular and Cellular Mechanisms of Loss of Residual Hearing after Cochlear Implantation

Jia¹,

Wang²,

François³

et al. 2013

Ann Otol Rhinol Laryngol

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“…Pharmacological treatment of the cochlea protects residual hearing in experimental settings. Previous studies show that dexamethasone significantly reduces hearing loss when applied as a single dose, either locally to the round window [James et al, 2008;Maini et al, 2009;Eastwood et al, 2010b] or systemically via intravenous injection [Connolly et al, 2011]. Nevertheless, the most effective route of administration in a clinical setting remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

et al. 2013

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Dexamethasone administered prior to cochlear implantation has been shown to reduce the loss of residual hearing in experimental settings. However, its effect on the tissue response around the implant has not been extensively studied. In this study dexamethasone sodium phosphate was administered to guinea pigs via local delivery to the round window (2% dexamethasone for 120 min prior to surgery, ‘local 2/120', or 20% dexamethasone for 30 min prior to surgery) or intravenously (2 mg/kg dexamethasone for 60 min) prior to implantation. Auditory brainstem responses (ABR) were monitored for 3 months, after which the cochleae were embedded in Spurr's resin and sectioned. The extent of the tissue response and the survival of the neurosensory structures were analysed. Both local 2/120 and systemically delivered dexamethasone improved ABR thresholds when compared with control animals. Systemic dexamethasone also reduced the tissue response around the electrode. This suggests that whilst both locally and systemically administered dexamethasone can protect residual hearing after cochlear implantation, their effects upon the tissue response to implantation may differ.

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Permanent and transient effects of locally delivered n-acetyl cysteine in a guinea pig model of cochlear implantation

Cited by 52 publications

References 54 publications

Relations between cochlear histopathology and hearing loss in experimental cochlear implantation

Relations between cochlear histopathology and hearing loss in experimental cochlear implantation

Molecular and Cellular Mechanisms of Loss of Residual Hearing after Cochlear Implantation

Effect of Both Local and Systemically Administered Dexamethasone on Long-Term Hearing and Tissue Response in a Guinea Pig Model of Cochlear Implantation

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