title: Morphological correlates of hearing loss after cochlear implantation and electro-acoustic stimulation in a hearing-impaired Guinea pig model.
abstract: Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 h of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not correlated with threshold shifts at any frequency. As in the previous study in a normal-hearing model, stria vascularis capillary changes were associated with immediate hearing loss after implantation, while little to no hair cell loss was observed even in cochlear regions with threshold shifts as large as 40-50 dB. These findings again support a role of lateral wall blood flow changes, rather than hair cell loss, in hearing loss after surgical trauma, and implicate the endocochlear potential as a factor in implantation-induced hearing loss. Further, the analysis of the hair cell ribbons and post-synaptic receptors suggest that delayed hearing loss may be linked to synapse or peripheral nerve loss due to stimulation excitotoxicity or inflammation. Further research is needed to separate these potential mechanisms of delayed hearing loss.
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: reiss@ohsu.edu.
authors.forename: Lina A J
authors.initials: LA
authors.lastname: Reiss
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Gemaine
authors.initials: G
authors.lastname: Stark
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Anh T
authors.initials: AT
authors.lastname: Nguyen-Huynh
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Kayce A
authors.initials: KA
authors.lastname: Spear
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China.
authors.forename: Hongzheng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Department of Communication Sciences and Disorders, John A. Burns School of Medicine, University of Hawai'i at Mānoa, 677 Ala Moana Blvd, Honolulu, HI 96816, USA.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold; D002196:Capillaries / Q000473:pathology; D003051:Cochlea / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D019929:Cochlear Implantation / Q000009:adverse effects* / Q000295:instrumentation; D003054:Cochlear Implants / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D004558:Electric Stimulation; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology; D006309:Hearing; D006317:Hearing Loss, Noise-Induced / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D011474:Prosthesis Design; D013316:Stria Vascularis / Q000473:pathology; D013569:Synapses / Q000473:pathology
keywords: Cochlear implant; Electro-acoustic stimulation; Hearing loss; Hybrid; Stria vascularis; Synapse