1. Cannula-based drug delivery to the guinea pig round window causes a lasting hearing loss that may be temporarily mitigated by BDNF.
- Author
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Sale PJP, Uschakov A, Saief T, Rowe DP, Abbott CJ, Luu CD, Hampson AJ, O'Leary SJ, and Sly DJ
- Subjects
- Acoustic Stimulation, Animals, Audiometry, Pure-Tone, Auditory Fatigue drug effects, Disease Models, Animal, Evoked Potentials, Auditory, Brain Stem drug effects, Guinea Pigs, Hearing Loss diagnostic imaging, Hearing Loss etiology, Hearing Loss physiopathology, Infusion Pumps, Implantable, Microscopy, Confocal, Perilymph chemistry, Recovery of Function, Round Window, Ear diagnostic imaging, Round Window, Ear physiopathology, Time Factors, Tomography, Optical Coherence, Brain-Derived Neurotrophic Factor administration & dosage, Catheterization instrumentation, Catheters, Indwelling, Central Venous Catheters, Drug Delivery Systems instrumentation, Hearing drug effects, Hearing Loss drug therapy, Round Window, Ear drug effects
- Abstract
Sustained local delivery of drugs to the inner ear may be required for future regenerative and protective strategies. The round window is surgically accessible and a promising delivery route. To be viable, a delivery system should not cause hearing loss. This study determined the effect on hearing of placing a drug-delivery microcatheter on to the round window, and delivering either artificial perilymph (AP) or brain-derived neurotrophic factor (BDNF) via this catheter with a mini-osmotic pump. Auditory brainstem responses (ABRs) were monitored for 4 months after surgery, while the AP or BDNF was administered for the first month. The presence of the microcatheter - whether dry or when delivering AP or BDNF for 4 weeks - was associated with an increase in ABR thresholds of up to 15 dB, 16 weeks after implantation. This threshold shift was, in part, delayed by the delivery of BDNF. We conclude that the chronic presence of a microcatheter in the round window niche causes hearing loss, and that this is exacerbated by delivery of AP, and ameliorated temporarily by delivery of BDNF., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
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