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- Title:
Effects of a dexamethasone-releasing implant on cochleae: A functional, morphological and pharmacokinetic study.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Liu, Ya; Jolly, Claude; Braun, Susanne; Janssen, Thomas; Scherer, Elias; Steinhoff, Jochen; Ebenhoch, Harald; Lohner, Andrea; Stark, Thomas; Kiefer, Jan
- Abstract:
- This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation.Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses.ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively.Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.
- Journal title abbreviation:
- Hear Res
- Year:
- 2015
- Journal volume:
- 327
- Pages contribution:
- 89-101
- Language:
- eng
- Fulltext / DOI:
- doi:10.1016/j.heares.2015.04.019
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/25987502
- Print-ISSN:
- 0378-5955
- TUM Institution:
- Hals-Nasen-Ohrenklinik und Poliklinik
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