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Aim: To explore morphological or electrophysiological evidence for the presence of endolymphatic hydrops (EH) in guinea pig cochleae in the first 3 months after cochlear implantation., Methods: Dummy silastic electrodes were implanted atraumatically into the basal turn of scala tympani via a cochleostomy. Round window electrocochleography (ECochG) was undertaken prior to and after implantation. Animals survived for 1, 7, 28 or 72 days prior to a terminal experiment, when ECochG was repeated. The cochleae were imaged using micro-CT after post-fixing with osmium tetroxide to reveal the inner ear soft tissue structure. EH was assessed by visual inspection at a series of frequency specific places along the length of the cochlea, and the extent to which Reissner's membrane departed from its neutral position was quantified. Tissue response volumes were calculated. Using ECochG, the ratio of the summating potential to the action potential (SP/AP ratio) was calculated in response to frequencies between 2 and 32 kHz., Results: There was minimal evidence of electrode trauma from cochlear implantation on micro-CT imaging. Tissue response volumes did not change over time. EH was most prevalent 7 days after surgery in implanted ears, as determined by visual inspection. Scala media areas were increased, as expected in cases of EH, over the first month after cochlear implantation. SP/AP ratios decreased immediately after surgery, but were elevated 1 and 7 days after implantation., Conclusions: EH is prevalent in the first weeks after implant surgery, even in the absence of significant electrode insertion trauma., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Clinically, gentamicin has been used extensively to treat the debilitating symptoms of Mèniére's disease and is well known for its vestibulotoxic properties. Until recently, it was widely accepted that the round window membrane (RWM) was the primary entry route into the inner ear following intratympanic drug administration. In the current study, gentamicin was delivered to either the RWM or the stapes footplate of guinea pigs (GPs) to assess the associated hearing loss and histopathology associated with each procedure. Vestibulotoxicity of the utricular macula, saccular macula, and crista ampullaris in the posterior semicircular canal were assessed quantitatively with density counts of hair cells, supporting cells, and stereocilia in histological sections. Cochleotoxicity was assessed quantitatively by changes in threshold of auditory brainstem responses (ABR), along with hair cell and spiral ganglion cell counts in the basal and second turns of the cochlea. Animals receiving gentamicin applied to the stapes footplate exhibited markedly higher levels of hearing loss between 8 and 32 kHz, a greater reduction of outer hair cells in the basal turn of the cochlea and fewer normal type I cells in the utricle in the vestibule than those receiving gentamicin on the RWM or saline controls. This suggests that gentamicin more readily enters the ear when applied to the stapes footplate compared with RWM application. These data provide a potential explanation for why gentamicin preferentially ablates vestibular function while preserving hearing following transtympanic administration in humans., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

Cochlear endolymph is maintained at a potential of (+)80 mV by an active transport mechanism involving the stria vascularis (SV). This so-called endocochlear potential (EP) is integral to hair cell transduction. We compared the EP with changes in SV area and Na(+),K(+)-ATPase expression following a sensorineural hearing loss. Guinea pigs were deafened using kanamycin and a loop diuretic, and the EP was measured at two, 14, 56, 112 or 224 days following deafening. Auditory brainstem responses were used to confirm that each animal had a severe-profound hearing loss. There was a significant reduction in EP following two days of deafness (normal, 73.5 mV S.E.M.=2.4; deaf, 42.1 mV, S.E.M.=2.8; P<0.0001, t-test). In animals deafened for 14 days the EP had partially recovered (65.2 mV, S.E.M.=5.08), while animals deafened for longer periods exhibited a complete recovery (56 days 80.5 mV, S.E.M.=5.36; 112 days 75.7 mV, S.E.M.=2.71; 224 days 81.0 mV; S.E.M.=6.0). Despite this recovery, there was a systematic reduction in SV area with duration of deafness over the first 112 days of deafness. Significant reductions were localised to the basal turn in animals deafened for two days, but had extended to all turns in animals deafened for 112 days. While there was a significant reduction in strial area, the optical density of Na(+),K(+)-ATPase within the remaining SV was normal. Since the treated animals exhibited essentially a complete elimination of all hair cells, the total K(+) leakage current from the scala media would be expected to be significantly reduced. The large reduction in the extent of the SV after deafening suggests that a reduced strial volume is capable of maintaining a normal EP under conditions of reduced K(+) leakage current.

Cisplatin, at 0, 3, 30 or 300 microg/ml in saline, was applied to the scala tympani of the cochlea of guinea pigs via osmotic mini-pumps, operating at a pump rate of 0.5 microl/h. Electrocochleographic recordings were made from an implanted round window electrode. When an electrocochleographic criterion of ototoxicity was reached (40 dB loss in compound action potential (CAP) threshold at 8 kHz), or after 1 week if this criterion was not reached, the animals were sacrificed for light microscopy. A subgroup of animals had endocochlear potentials (EPs) measured prior to sacrifice. Hearing remained stable in the 0 microg/ml control group, but a sudden drop of auditory sensitivity across the whole frequency range was observed in all other groups. It took 1-5 days before the drop occurred, dependent on cisplatin concentration. CAP and cochlear microphonics were lost simultaneously. The EP was severely depressed in the affected animals, suggesting that cisplatin effects on the EP are primary. However, histology revealed an accompanying loss of outer hair cells, primarily in the basal turn. It is concluded that if cisplatin is given until ototoxicity becomes apparent electrophysiologically, then the cochlear pathology from intrascalar cisplatin administration resembles that from daily parenteral administration at 1.5-2.0 mg/kg. The cochlear pathology from the parenteral treatment was greater than that observed with 30 microg/ml pumps, and less than that from 300 microg/ml pumps.

Extracellular responses of dorsal cochlear nucleus single units were recorded in response to biphasic, bipolar electrical stimulation of spiral ganglion cells and their peripheral processes using a banded electrode array in the scala tympani of the barbiturate anaesthetised cat. The DCN responses to this stimulus were the result of excitatory and suppressive (including inhibitory) processes. The excitatory responses from DCN units were usually within a range of 1.8-2.8 ms and these responses were probably the result of monosynaptic input from the auditory nerve. Latencies > 2.8 ms were most likely due to activation of di- and poly-synaptic pathways from auditory nerve fibres, except that latencies between 3.5-4.75 in hearing animals could have arisen from electrophonic mechanisms. Suppression of spontaneous activity was usually long acting, lasting > 70 ms following each pulse of the pulse train, but short acting suppression with a latency of 3.5-4.75 ms and a duration of < 10 ms was occasionally observed. These suppressive responses probably resulted from synaptic inhibitory input, but neural membrane properties may have contributed. In hearing animals, excitatory latencies within the range 1.8-5.2 ms were similar for units with different response area types or different PSTH patterns in response to acoustic CF tones or noise.

The current distribution of bipolar electrodes implanted into the scala tympani of the cat cochlea was investigated using a two-electrode masking technique. Two electrode masking is a non-invasive technique which requires two electrically independent electrodes and relies upon the forward masking of the electrically evoked brainstem response to a probe stimulus by that of a preceding test stimulus. The technique was described in terms of a model, which enabled an approach for estimating the scala tympani length constant to be established. Model results have shown good agreement with electrophysiological results. Application of the model confirmed the scala tympani length constant within the basal turn of the cochlea to lie between 3 and 4 mm.