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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ItemA single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support( 2005)Unavailable due to copyright.
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ItemDelivery of neurotrophin-3 to the cochlea using alginate beads( 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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ItemTracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea( 2004)Unavailable due to copyright.