Graeme Clark Collection
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ItemSynergy between TGF-ß3 and NT-3 to promote the survival of spiral ganglia neurones in vitro( 1998)Transforming growth factor-βs (TGF-βs) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-βs and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-βs supports neuronal survival in a concentration-dependent manner. Moreover TGF-βs and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.
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ItemEffects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens( 1998)We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.
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ItemDirect current measurements in cochlear implants: an in vivo and in vitro study( 1998)Direct current (DC) was measured both in vivo and in vitro in cochlear implant electrodes with stimulation at moderate to high pulse rates in monopolar and bipolar modes. In vivo DC was approximately 2-3 times higher than that measured in vitro. In vivo DC levels were <100 nA even at very high rates, although DC levels increased as a function of stimulus rate and charge intensity. DC levels were lower: in the monopolar than in the bipolar stimulation condition. Stimulation with a monopolar capacitively coupled extracochlear electrode showed even lower DC levels in the intracochlear .electrodes. Our results indicated that the Nucleus electrode shorting system is able to maintain a low level of DC during very high rate stimulation for both monopolar and bipolar modes.
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ItemChanges in excitability of the auditory nerve following electrical stimulation using large surface area electrodes [Abstract]( 1998)High rate intracochlear electrical stimulation at intensities well above clinical limits can induce significant reductions in the excitability of the auditory nerve. Such changes are primarily associated with stimulus induced neuronal activity, although direct current (DC) can also contribute. In the present study we examined the extent of stimulus induced change in auditory nerve excitability using large surface area platinum (Pt) electrodes (high-Q). These electrodes have an effective surface area 10-20 times larger than standard Pt electrodes, resulting in lower DC and charge density for a common stimulus. Twenty-three guinea pigs anaesthetized with ketamine (40 mg/kg i.p.) and xylazine (4 mg/kg i.p.), were bilaterally implanted with either high-Q or standard Pt electrodes, and unilaterally stimulated for two hours using a stimulus intensity of 0.34 μC/phase at stimulus rates of 200,400, or 1000 pulses/s (pps). Electrically evoked auditory brainstem responses (EABRs) were recorded before and periodically following the acute stimulation. No reduction in EABR amplitude was observed at 200 pps for both stimulating electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. At 200 pps there was no significant difference (p>0.05 ANOVA) in the post-stimulus recovery of EABR amplitudes following stimulation with either high-Q or standard Pt electrodes. There was, however, significantly greater EABR recovery following stimulation with the high-Q electrode compared with the standard Pt electrode at 400 (p<0.05) and 1000 pps (p<0.05). These data indicate that large surface area high-Q electrodes can significantly reduce stimulus induced changes in auditory nerve excitability, and may therefore have important clinical application.
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ItemChronic electrical stimulation of the auditory nerve using non-charge balanced stimuli [Abstract]( 1998)Cochear implants use charge balanced biphasic current pulses and electrode shorting between current pulses to minimise potentially damaging direct current (DC). In the present study we evaluated the effectiveness of the electrode shorting technique using a non-charge balanced stimulus regime. Under general anaesthesia (ketamine (20 mg/kg. i.m.) and xylazine (3.8 mg/kg. i.m)), eight normal hearing cats were bilaterally implanted with two channel platinum scala tympani electrodes. Each animal was stimulated unilaterally for 500 to 2200 h using 50 μs monophasic current pulses. The stimuli were delivered at rates of 500 or 2000 pulses per channel continuously at mid-dynamic range intensities. Electrically-evoked auditory brainstem responses (EABR) were periodically recorded to monitor the status of the auditory nerve and to ensure stimulus intensity remained above threshold. At a stimulus rate of 500 pulses/s, electrode shorting effectively reduced DC levels to ≤ 0.3µA. Longitudinal EABR's recorded from these animals , remained relatively stable over the stimulus duration. These cochleae showed minimal tissue response and there was no statistically significant difference in spiral ganglion cell density when compared with controls (p=0.21, Mann-Whitney U-test). Chronic stimulation at 2000 pulses/s resulted in increased DC levels (0.6-2.8µA). These cochleae exhibited a highly significant reduction in spiral ganglion cell density when compared with controls (p<0.0001), and their EABR's typically displayed an elevation in threshold as a function of stimulus duration. The present findings indicate that continuous non-charge balanced stimuli at rates of 2000 pulses/s can result in significant loss of spiral ganglion cells, presumably as a result of increased DC levels.
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ItemElectrical stimulation of the auditory nerve: chronic monopolar stimulation using very high stimulus rates [Abstract]( 1998)Speech processing strategies based on high rate electrical stimulation have been associated with recent improvements of speech perception among cochlear implant users. In the present study we investigated the effects of chronic monopolar stimulation using very high rates (14493 pulses\s). Under general anaesthesia (ketamine (20 mg/kg) and xylazine (3.8 mg/kg) i.p.) six normal hearing cats were implanted bilaterally with a three channel platinum (Pt) scala tympani electrode array, while a return Pt-electrode was placed outside the bulla. Chronic electrical stimulation using charge-balanced biphasic current pulses was delivered unilaterally via a transcutaneous leadwire connected to a backpack-stimulator for up to 2000 h. The animals hearing status was periodically monitored using acoustically evoked compound action potentials (CAP's) and brainstem responses (ABR's). In addition the electrically evoked ABR (EABR) was also recorded to ensure that the chronic stimulus was above threshold. Stimulus current and electrode voltage waveforms were monitored twice daily and access resistance (Ra) and electrode impedance (Zc) calculated. ABR and CAP thresholds were elevated immediately following implantation, but generally showed evidence of partial recovery (0-40 dB). Further deterioration of thresholds on the stimulated side (10-30 dB) was subsequently observed, while control-thresholds remained more stable. Ra (1.3-1.8 kΩ) and Zc (2.2-3.8Ω) typically increased in the first few weeks of electrical stimulation up to Ra:5.6 kΩ and Zc:8.1 kΩ, before decreasing slightly to a constant plateau. These initial results indicate changes in the electrode-tissue interface and tissue growth within the cochlea. They also indicate that chronic stimulation at these high rates may decrease residual hearing.