Graeme Clark Collection

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    Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
    Evans, AJ ; Thompson, BC ; Wallace, GG ; Millard, R ; O'Leary, SJ ; Clark, GM ; Shepherd, RK ; Richardson, RT (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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    Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons
    Richardson, RT ; Wise, AK ; Thompson, BC ; Flynn, BO ; Atkinson, PJ ; Fretwell, NJ ; Fallon, JB ; Wallace, GG ; Shepherd, RK ; Clark, GM ; O'Leary, SJ (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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    Speech perception as a function of electrical stimulation rate: using the nucleus 24 cochlear implant system
    Vandali, Andrew E. ; Whitford, Lesley A. ; Plant, Kerrie L. ; Clark, Graeme M. ( 2000)
    Objective: To investigate the effect of varying electrical stimulation rate on speech comprehension by cochlear implant users, while keeping the number of stimulated channels constant. Design: Three average rates of electrical stimulation,250, 807, and 1615 pulses per second per channel (pps/ch), were compared using a speech processing strategy that employed an electrode selection technique similar to that used in the Spectral Maxima Sound Processor strategy (McDermott, McKay,& Vandali, 1992; McDermott & Vandali, Reference Note 1; McKay, McDermott, Vandali, & Clark, 1991)and the Spectral Peak strategy (Skinner et al., 1994;Whitford et al., 1995). Speech perception tests with five users of the Nucleus 24 cochlear implant system were conducted over a 21-wk period. Subjects were given take-home experience with each rate condition. A repeated ABC evaluation protocol with alternating order was employed so as to account for learning effects and to minimize order effects. Perception of open-set monosyllabic words in quiet and open-set sentences at signal to noise ratios ranging from +20 to 0 dB, depending on the subject’s ability, were tested. A comparative performance questionnaire was also administered. Results: No statistical differences in group performance between the 250 and 807 pps/ch rates were observed in any of the speech perception tests. However, significantly poorer group performance was observed for the 1615 pps/ch rate for some tests due predominantly to the results of one subject. Analysis of individual scores showed considerable variation across subjects. For some subjects, one or more of the three rate conditions evaluated provided benefits on some speech perception tasks. The results of the comparative performance questionnaire indicated a preference for the 250 and 807pps/ch rates over the 1615 pps/ch rate for most listening situations. Conclusions: For the speech processing strategy, implant system, and subjects evaluated in this study, the group results indicated that the use of electrical stimulation rates higher than 250 pps/ch (up to 1615 pps/ch) generally provided no significant improvement to speech comprehension. However, individual results indicated that perceptual.