Graeme Clark Collection
Permanent URI for this collection
Search Results
1 - 8 of 8
-
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.
-
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.
-
ItemDischarge rate-level functions from dorsal cochlear nucleus single units in response to acoustic and electrical stimulation of the auditory nerve( 1995)Discharge rate-level (I/O) functions possessed by dorsal cochlear nucleus (DCN) units were examined, in response to bipolar electrical stimulation of the cochlea of the barbiturate-anesthetized cat. Spontaneously active units usually possessed nonmonotonic functions with a minimum, and spontaneously inactive units usually possessed monotonic functions or nonmonotonic functions with a maximum (NM+). In response to acoustic high-pass filtered noise, the function relating discharge rate and cut off frequency resembled the same unit's I/O function to electrical stimulation. The I/O functions to acoustic characteristic tones were usually monotonic or NM+. These results suggest that in the DCN, a prerequisite for the generation of acoustic-like responses with an electrical stimulus may be the matching of the cochlear place and spatial extent activated by each stimulus.
-
ItemIntracochlear electrical simulation of normal and deaf cats investigated using brainstem response audiometry( 1983)Brainstem response audiometry for intracochlear electrical stimulation of normal-hearing and deafened cats was investigated. In normal cochleas the brainstem response amplitude grew slowly near threshold as a current-amplitude dependent process, identified as electrophonic in origin. This terminated in a rapidly growing charge-dependent process at approximately 20 dB above threshold, identified as direct electrical stimulation of the auditory nerve. Small levels of white noise (25-35 dB SPL) were sufficient to mask most of the electrophonic response, leaving the direct stimulation process essentially unmodified. In cochleas damaged with d.c. currents and loud sounds, only a rapidly growing charge-dependent process was observed which grew similarly to that in normal-hearing cats but occurred at lower currents. This indicates that possibly the electrical properties of the cochlea were altered in the deafening process, suggesting the inadequacy of normal animals as deaf models for electrical stimulation. Using the technique of derived brainstem responses, it was shown that direct electrical stimulus components were localized to the vicinity of the stimulus electrode with electrophonic components distributed more widely. However, at high currents there was some evidence of the stimulus spreading into the internal auditory meatus.
-
ItemThe auditory brainstem response in hearing and deaf cats evoked by intracochlear electrical stimulation(Monash University Press, 1983)This study was performed to investigate in detail the auditory brainstem response (ABR) for intracochlear electrical stimulation. Brainstem response audiometry is a simple, noninvasive procedure with the responses under many stimulus conditions being readily understood in terms of single auditory nerve discharge properties. The amplitude and latency behaviour of the Nl brainstem response correlates well with that recorded directly from the auditory nerve (Huang & Buchwald, 1978). In addition, the brainstem response can be divided into frequency-specific components corresponding to tonotopical locations in the cochlea, as exhibited in the method of derived responses (e.g. Parker &Thornton, 1978). It is therefore well suited to both physiological and clinical investigation of auditory function and therefore should be useful in evaluating auditory function under conditions of electrical stimulation of the cochlea.
-
ItemPrediction of variance in neural response to cochlear implant stimulation and its implications for perception [Abstract]( 1997)Cochlear implant patients' perception of sound is derived via electrical pulses arising from an electrode array. Chosen aspects of the acoustic spectrum are coded via a stimulation pattern designed according to some sound coding algorithm. Thus, a patients' ability to discriminate between sounds, and in turn their understanding, is directly related to their ability to differentiate between the patterns of electrical stimulation which code various sounds.
-
ItemAn improved model of electrical stimulation of the auditory nerve(Monduzzi Editore, 1997)Mathematical models are a useful means of formally describing and investigating pertinent features of complex systems such as the human auditory system. These features may be deduced from physiological and psychophysical experiments utilising animal models or humans, and from engineering studies. Historically, models of the auditory nerve's (AN) response to electrical stimulation have ignored randomness in single-fiber activity which has been recorded in physiological studies. These models, however, have been unable to accurately predict a number of important psychophysical phenomena. In this study, a model that incorporates random activity of the AN is presented, and is shown to predict psychophysical performance. These results indicate that random activity is indeed an important part of the response of the AN to electrical stimulation.
-
ItemResponses from single units in the dorsal cochlear nucleus to electrical stimulation of the cochlea( 1992)To help improve our understanding of how the brain responds to electrical stimulation of the auditory nerve we have examined the responses of dorsal cochlear nucleus (DCN) units to both acoustic stimulation and electrical stimulation of the cochlea. This work extended our previous studies which have compared the responses to electrical and acoustic stimulation In the auditory nerve (Javel et al 1987, Ann. Otol. Rhinol. laryngeal. Suppl. 128, 96:2630) and the ventral cochlear nucleus (Shepherd et al 1988, NIH Contract NO1-NS-72342, 5th Quarterly Progress Report).