Graeme Clark Collection

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    Midbrain responses to micro-stimulation of the cochlea using high density thin-film arrays
    Allitt, BJ ; Morgan, SJ ; Bell, S ; Nayagam, DAX ; Arhatari, B ; Clark, GM ; Paolini, AG (ELSEVIER SCIENCE BV, 2012-05)
    A broader activation of auditory nerve fibres than normal using a cochlear implant contributes to poor frequency discrimination. As cochlear implants also deliver a restricted dynamic range, this hinders the ability to segregate sound sources. Better frequency coding and control over amplitude may be achieved by limiting current spread during electrical stimulation of the cochlea and positioning electrodes closer to the modiolus. Thin-film high density microelectrode arrays and conventional platinum ring electrode arrays were used to stimulate the cochlea of urethane-anaesthetized rats and responses compared. Neurophysiological recordings were taken at 197 multi-unit clusters in the central nucleus of the inferior colliculus (CIC), a site that receives direct monaural innervation from the cochlear nucleus. CIC responses to both the platinum ring and high density electrodes were recorded and differences in activity to changes in stimulation intensity, thresholds and frequency coding of neural activation were examined. The high density electrode array elicited less CIC activity at nonspecific frequency regions than the platinum ring electrode array. The high density electrode array produced significantly lower thresholds and larger dynamic ranges than the platinum ring electrode array when positioned close to the modiolus. These results suggest that a higher density of stimulation sites on electrodes that effectively 'aim' current, combined with placement closer to the modiolus would permit finer control over charge delivery. This may equate to improved frequency specific perception and control over amplitude when using future cochlear implant devices.
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    A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support
    Richardson, Rachael T. ; O'LEARY, STEPHEN ; Wise, Andrew ; Hardman, Jennifer ; Clark, Graeme M. ( 2005)
    Unavailable due to copyright.
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    Delivery of neurotrophin-3 to the cochlea using alginate beads
    Noushi, Fanoosh ; Richardson, Rachael T. ; Hardman, Jennifer ; Clark, Graeme M. ; O'LEARY, STEPHEN ( 2005)
    Objective: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. Background: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutical role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can he placed at the round window or inside the cochlea. This study investigates the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. Methods: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which surviva1 of auditory neurons was assessed. Results: Enzyme-linked immunosorbent assay studies demonstrated a 98%: to 99% loading of NT-3 with a slow, partial release over 5 days in Ringers solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction NT-3 loaded beads implanted as both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. Conclusions: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.
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    Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea
    Richardson, Rachael T. ; Wise, Andrew ; O'LEARY, STEPHEN ; Hardman, Jennifer ; Casley, David ; Clark, Graeme M. ( 2004)
    Unavailable due to copyright.