Graeme Clark Collection
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ItemPromoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes(WILEY, 2009-10)Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over 7 days. A 3-day SGN explant assay found that neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p < 0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge, and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
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ItemNo Preview AvailablePolypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons(ELSEVIER SCI LTD, 2009-05)Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm2 cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p<0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.
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ItemChronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study( 1997)A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 µs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms oft) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program, All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P=0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P=0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.
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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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ItemElectrical stimulation of residual hearing in the implanted cochlea( 1995)The average profoundly deaf person using a cochlear implant can now understand more speech than some severely to profoundly deaf people who use a hearing aid. For this reason there will be an increasing need to consider implanting people with residual hearing. In many of these people there could be significant hearing in the operated ear, as a majority of severely to profoundly deaf people are likely to have a symmetrical hearing loss. When three frequency average hearing thresholds were measured on 219 pensioners from the Australian National Acoustic Laboratories (H. Dillon, unpublished findings), 64% had less than a 10-dB difference between thresholds in each ear.
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ItemChronic electrical stimulation of the auditory nerve at high stimulus rates: preliminary results( 1994)The present preliminary report describes the electrophysiological response of the cochlea during long-term stimulation. The data indicate that electrical stimulation at a rate of 1000 pulses per second does not appear to adversely affect the implanted cochlea.
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ItemCochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens( 1992)The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 µC cm^-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult.
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ItemA physiological investigation of chronic electrical stimulation with scala tympani electrodes in kittens( 1992)A physiological investigation of cochlear electrical stimulation was undertaken in six two-month-old kittens. The scala tympani electrodes were implanted and electrically stimulated using biphasic balanced electrical pulses' for periods of 1000-1500h in four ears. Four ears received implants for same period but without electrical stimulation. The other two ears served as normal control. The results indicated: 1) Chronic electrical stimulation of the cochlea within electrochemically safe limits did not influence the hearing of kittens and the normal delivery of impulses evoked by acoustic and electrical signals on the auditory brainstem pathway. 2) The wave shapes of EABRs were similar to those of ABRs. The aptitudes of EABRs showed a significant increase following chronic electrical stimulation, resulting in a leftward shift in the input/ output function. The absolute latencies and interwave latencies of waves II-III , III -IV and II -IV were significantly shorter than those of ABRs. These results imply that there was no adverse effect of chronic electrical stimulation on the maturing auditory systems of kittens using these electrical parameters and the mechanism of electrical hearing should be further studied.
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ItemThe histopathological effects of chronic electrical stimulation of the cat cochlea(Cambridge University Press, 1983)The success of a cochlear implant depends on stimulating an adequate number of viable spiral ganglion cells. The effect of chronic electrical stimulation on ganglion cells is therefore an important consideration when assessing the effectiveness and safety of such a device. The histopathological assessment of chronic unstimulated intracochlear electrodes is now well documented (Simmons, 1967; Clark, 1973; Clark et al, 1975; Schindler and Merzenich, 1974; Schindler, 1976; Schindler et al, 1977; Sutton et al, 1980). These experimental studies have used a variety of electrode designs, materials and surgical techniques. However, all have shown that chronic implantation has little effect on the peripheral nerves and the spiral ganglion cells adjacent to an implant, provided the insertion procedure is free of trauma and infection.
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ItemChronic electrical stimulation of the auditory nerve in cats: physiological and histopathological results( 1983)The ability of spiral ganglion cells to survive long-term electrical stimulation is a precondition for the success of cochlear prostheses. In this study 10 cats were implanted bilaterally with bipolar scala tympani electrodes and stimulated for periods of up to 2029 hours using charge balanced biphasic current pulses. The status of the auditory nerve was monitored periodically by recording electrically evoked auditory brainstem responses. At the conclusion of the stimulation program, spiral ganglion cell survival was assessed for stimulated and control cochleas; comparison of the two groups showed no statistically significant difference. The results of this study indicate that long-term intracochlear electrical stimulation using carefully controlled biphasic pulses does not adversely affect the spiral ganglion cell population.