Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs

Benjamin Philipp Ernst; Ulf-Rüdiger Heinrich; Mathias Fries; Regina Meuser; Tobias Rader; Jonas Eckrich; Roland H Stauber; Sebastian Strieth

doi:10.3389/fncel.2023.1189980

Cochlear implantation impairs intracochlear microcirculation and counteracts iNOS induction in guinea pigs

Front Cell Neurosci. 2023 Jun 28:17:1189980. doi: 10.3389/fncel.2023.1189980. eCollection 2023.

Authors

Benjamin Philipp Ernst^#¹, Ulf-Rüdiger Heinrich^#², Mathias Fries¹, Regina Meuser³, Tobias Rader⁴, Jonas Eckrich², Roland H Stauber², Sebastian Strieth¹

Affiliations

¹ Department of Otorhinolaryngology, University Medical Center Bonn (UKB), Bonn, Germany.
² Department of Otorhinolaryngology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
³ Institute for Medical Biometry, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
⁴ Division of Audiology, Department of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-Universität München (LMU), Munich, Germany.

^# Contributed equally.

Abstract

Introduction: Preservation of residual hearing remains a great challenge during cochlear implantation. Cochlear implant (CI) electrode array insertion induces changes in the microvasculature as well as nitric oxide (NO)-dependent vessel dysfunction which have been identified as possible mediators of residual hearing loss after cochlear implantation.

Methods: A total of 24 guinea pigs were randomized to receive either a CI (n = 12) or a sham procedure (sham) by performing a cochleostomy without electrode array insertion (n = 12). The hearing threshold was determined using frequency-specific compound action potentials. To gain visual access to the stria vascularis, a microscopic window was created in the osseous cochlear lateral wall. Cochlear blood flow (CBF) and cochlear microvascular permeability (CMP) were evaluated immediately after treatment, as well as after 1 and 2 h, respectively. Finally, cochleae were resected for subsequent immunohistochemical analysis of the iNOS expression.

Results: The sham control group showed no change in mean CBF after 1 h (104.2 ± 0.7%) and 2 h (100.8 ± 3.6%) compared to baseline. In contrast, cochlear implantation resulted in a significant continuous decrease in CBF after 1 h (78.8 ± 8.1%, p < 0.001) and 2 h (60.6 ± 11.3%, p < 0.001). Additionally, the CI group exhibited a significantly increased CMP (+44.9% compared to baseline, p < 0.0001) and a significant increase in median hearing threshold (20.4 vs. 2.5 dB SPL, p = 0.0009) compared to sham after 2 h. Intriguingly, the CI group showed significantly lower iNOS-expression levels in the organ of Corti (329.5 vs. 54.33 AU, p = 0.0003), stria vascularis (596.7 vs. 48.51 AU, p < 0.0001), interdental cells (564.0 vs. 109.1 AU, p = 0.0003) and limbus fibrocytes (119.4 vs. 18.69 AU, p = 0.0286).

Conclusion: Mechanical and NO-dependent microvascular dysfunction seem to play a pivotal role in residual hearing loss after CI electrode array insertion. This may be facilitated by the implantation associated decrease in iNOS expression. Therefore, stabilization of cochlear microcirculation could be a therapeutic strategy to preserve residual hearing.

Keywords: cochlea implantation; cochlear microcirculation; hearing preservation; iNOS; microvascular permeability; nitric oxide.

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG grant STR1014), the Intramural Biomaterials, Tissues and Cells in Science (BiomaTiCS) Program of the University Medical Center Mainz, Germany as well as MED-EL GmbH (Innsbruck, Austria).