Permanent and transient effects of locally delivered n-acetyl cysteine in a guinea pig model of cochlear implantation
ABSTRACT Protection of residual hearing after cochlear implant surgery can improve the speech and music perception of cochlear implant recipients, particularly in the presence of background noise. Surgical trauma and chronic inflammation are thought to be responsible for a significant proportion of residual hearing loss after surgery. Local delivery of the anti-oxidant precursor n-acetyl cysteine (NAC) to the cochlea via round window 30min prior to surgery, increased the level of residual hearing at 24-32kHz 4weeks post surgery compared to controls. The hearing protection was found in the basal turn near the site of implantation. Coincidentally, the basal turn was also the location that sustained the greatest hearing loss. As well as protecting residual hearing, NAC-treated animals demonstrated a reduction in the chronic inflammatory changes associated with implantation. While these findings indicate that anti-oxidant therapy can be used to reduce the hearing loss associated with surgical trauma, the local delivery of NAC was associated with a transient increase in hearing thresholds, and osseoneogenesis was seen in a greater number of NAC-treated animals. These side-effects would limit its clinical use through local cochlear administration. However, it is not known yet whether these effects would also be produced by other anti-oxidants, or ameliorated by using a different route of administration.
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ABSTRACT: 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 2-32 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 hour before implantation, 2) Local dexamethasone, 2% applied topically to the round window for 30 minutes prior to cochlear implantation, 3) Local n-acetyl cysteine, 200 μg applied topically to the round window for 30 minutes 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.Hearing research 02/2013; 298. DOI:10.1016/j.heares.2013.01.012 · 2.85 Impact Factor
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ABSTRACT: Delivery of intramuscular injection of methylprednisolone around the implantation surgery improved the hearing threshold shift induced by cochlear implantation. During electroacoustic cochlear implantation surgery, the residual hearing is not preserved in about 15% of cases. In this study, we tested the effects of intramuscular administration of methylprednisolone on the hearing loss induced by cochlear implantation in a model of guinea pig cochlear implantation. Eleven guinea pigs with normal hearing were implanted with a 254 μm diameter silicone array through a cochleostomy, and the effects on hearing of longstanding array insertion (21 days) were assessed. Six of the implanted animals received intramuscular administration of methylprednisolone. Auditory brainstem response recordings were performed before and up to 21 days after the cochlear implantation. CT scans were performed in some animals 1 month after implantation. CT scans confirmed that the array was well positioned in tested animals. From days 3 to 21, a hearing loss of about 30 dB on all frequencies was observed in the implanted nontreated group. This hearing loss remained stable during the whole follow-up period. Compared with implanted nontreated animals, the hearing threshold shift decreased by 12 dB in animals treated with methylprednisolone.Acta oto-laryngologica 12/2010; 131(6):579-84. DOI:10.3109/00016489.2010.541936 · 0.99 Impact Factor