Effect of both local and systemically administered dexamethasone on long-term hearing and tissue response in a Guinea pig model of cochlear implantation.

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.

Pre-operative intravenous dexamethasone prevents auditory threshold shift in a guinea pig model of cochlear implantation.

AIM: To protect hearing during cochlear implantation with systemic administration of dexamethasone. METHODS: Seventeen normal-hearing guinea pigs were randomly allocated to receive an intravenous injection of either normal saline (control), low- (0.2 mg/kg) or high- (2 mg/kg) dose dexamethasone 60 min prior to cochlear implantation. Auditory brainstem response (ABR) threshold shifts (2-32 kHz) were estimated between pre- and 4-week-postoperative levels. RESULTS: ABR threshold shifts (8-32 kHz) observed in control and low-dose steroid groups were significantly reduced in the high-dose steroid group. CONCLUSIONS: A single, high-dose injection of intravenous dexamethasone protected hearing during cochlear implantation.

Targeted therapy of the inner ear.

BACKGROUND: There is experimental evidence that targeted delivery of steroids to the inner ear can protect hearing during cochlear implant surgery. The best protection appears to be achieved through pre-treatment of the cochlea, but the time period required for treatment is long compared with the duration of surgery, and needs further optimization. The stability of hearing thresholds is determined over a 3-month period after hearing preservation cochlear implantation. METHODS: Adult guinea pigs were implanted with a miniature cochlear implant electrode, and pure tone auditory brainstem response (ABR) thresholds were estimated in response to pure tones of 2-32 kHz immediately after surgery and at 1 week, 1 month and 3 months. Spiral ganglion cell (SGC) densities were estimated from mid-modular histological sections of the cochlea. Thirty minutes prior to implantation, a polymeric sponge (Seprapack, Genzyme) was loaded with either a 2% solution of dexamethasone phosphate or normal saline (control) and placed onto the round window. RESULTS: Implantation was associated with an immediate elevation in thresholds across frequencies, with a full recovery below 2 kHz over the next week and a partial recovery of thresholds at higher frequencies. These thresholds remained unchanged for the next 3 months. There was an immediate and sustained reduction in the elevation of thresholds at 32 kHz in dexamethasone-treated animals. SGC densities were greater in steroid-treated animals than controls in the basal turn of the cochlea (at the region of implantation) 3 months after implantation. CONCLUSION: It is concluded that ABR thresholds remain stable for 3 months after cochlear implantation in the guinea pig, and that local application of steroids to the inner ear prior to implantation is an effective method of preserving SGC populations when there is residual hearing at the time of implantation.

Early cochlear response and ICAM-1 expression to cochlear implantation.

AIM: To examine the early cochlear response and intercellular cell adhesion molecule-1 (ICAM-1) expression to implantation of a cochlear electrode into the scala tympani. BACKGROUND: Understanding the early response of the cochlea to implantation may inform the duration which drug therapies should be delivered to protect hearing. METHODS: Guinea pigs were implanted with a cochlear electrode and survived 1, 2, or 7 days before they were euthanized, cochleae harvested, processed, and cryosectioned for light microscopy or ICAM-1 immunohistochemistry. RESULTS: On hematoxylin and eosin staining, scala tympani was characterized by the presence of fibrin and blood clot at 1 to 2 days after surgery, with a leukocytic infiltrate, primarily of neutrophils and macrophage-like cells. By 7 days after surgery, fibroblasts had infiltrated the clot, and the numbers of red blood cells (RBCs) and neutrophils had diminished. ICAM-1 expression was greatest in the lateral cochlear wall with highest expression found in the basal turn in the region of the electrode at 24 hours postimplantation. CONCLUSION: The cochlear vasculature is maximally primed to recruit cells from the circulation, as evidenced by ICAM-1 expression levels, at 24 hours after cochlear implantation. This response is similar to that seen after other types of injury. Where cochlear implantation differs is the predominance of fibrin and clot early after electrode insertion before infiltration by fibroblasts by the end of the first postoperative week. These results suggest that anti-inflammatory drugs aimed at reducing the extravasation of immunecompetent cells into the cochlea must be effective over the first few days after surgery. Whether this can be achieved through preoperative treatment alone, or whether therapy will need to continue postoperatively, awaits further experimentation.

Systemic immunity influences hearing preservation in cochlear implantation.

HYPOTHESIS: To determine whether a systemic immune response influences hearing thresholds and tissue response after cochlear implantation of hearing guinea pigs. METHODS: Guinea pigs were inoculated with sterile antigen (Keyhole limpet hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem response thresholds were performed before implantation and 1 and 4 weeks later. Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid carboxymethylcellulose sponge and was applied to the round window for 30 minutes before electrode insertion. Normal saline was used for controls. Cochlear histology was performed at 4 weeks after implantation to assess the tissue response to implantation. To control for the effect of keyhole limpet hemocyanin priming, a group of unprimed animals underwent cochlear implantation with a saline-soaked pledget applied to the round window. RESULTS: Keyhole limpet hemocyanin priming had no significant detrimental effect on thresholds without implantation. Thresholds were elevated after implantation across all frequencies tested (2-32 kHz) in primed animals but only at higher frequencies (4-32 kHz) in unprimed controls. In primed animals, dexamethasone treatment significantly reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the more frequent observation of lymphocytes in the tissue response to the implant. CONCLUSION: Systemic immune activation at the time of cochlear implantation broadened the range of frequencies experiencing elevated thresholds after implantation. Local dexamethasone provides partial protection against this hearing loss, but the degree and extent of protection are less compared to previous studies with unprimed animals.

Round window delivery of dexamethasone ameliorates local and remote hearing loss produced by cochlear implantation into the second turn of the guinea pig cochlea.

Application of dexamethasone to the round window has been shown to ameliorate high frequency hearing loss resulting from the trauma of cochlear implantation in experimental animals, but elucidation of the factors influencing protection of the high frequencies has been confounded by the local trauma from electrode array insertion. In this experiment, a second turn cochleostomy and implantation was performed on guinea pigs, to examine protection in the basal turn without the confounding effect of local trauma, as well as to test the efficacy of hearing protection in the second cochlear turn. The implantation resulted in an increase in hearing thresholds across all frequencies examined (2-32 kHz). Local delivery of dexamethasone to the round window prior to implantation protected hearing across frequencies from 2 to 32 kHz. Auditory thresholds improved over the first week after surgery, and then remained stable for the month of the experiment. The protection of hearing in the basal turn increased with longer periods of drug application prior to implantation. The level of hearing protection in the second turn was similar irrespective of the time that the drug was applied, but was greater when a higher steroid concentration was used. It was concluded that steroids protect hearing in the basal turn of the cochlea even when there was no local trauma. The level of hearing protection in the second turn exceeded that expected from models of steroid diffusion through the cochlea, suggesting that inner ear surgery alters the distribution of dexamethasone within the cochlea.