title: Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study.
abstract: We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Bas
authors.affiliation: Biomedical Engineering, College of Engineering, University of Miami, Coral Gables, FL, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Bohorquez
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Goncalves
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Perez
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Christine T
authors.initials: CT
authors.lastname: Dinh
authors.affiliation: MED-EL Hearing Implants, Innsbruck, Austria.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Garnham
authors.affiliation: MED-EL Hearing Implants, Innsbruck, Austria.
authors.forename: Roland
authors.initials: R
authors.lastname: Hessler
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Adrien A
authors.initials: AA
authors.lastname: Eshraghi
authors.affiliation: Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: tvandewater@med.miami.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Van De Water
mesh_terms: D000818:Animals; D003051:Cochlea / Q000502:physiology / Q000601:surgery; D019929:Cochlear Implantation / Q000009:adverse effects* / Q000379:methods*; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004566:Electrodes / Q000009:adverse effects*; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology*; D006309:Hearing; D008297:Male; D009474:Neurons / Q000473:pathology*; D012533:Scala Tympani / Q000502:physiology; D012828:Silicones / Q000737:chemistry; D013314:Stress, Mechanical
chemical_list: D012828:Silicones; D003907:Dexamethasone
keywords: Cochlear implantation; Hair cell loss; Hearing loss; Increased impedance; Insertion trauma; Local delivery of dexamethasone; Otoprotection