Protecting against electrode insertion trauma using dexamethasone

Abstract

Objective: To compare the benefits of a dexamethasone-eluting array for hearing preservation and cochlear histopathology in low trauma (soft-surgery) and high trauma models of cochlear implant surgery.

Methods: Adult guinea pigs were implanted with an intra-cochlear array using two different surgical procedures: either a soft-surgery approach or following generation of electrode insertion trauma (high trauma). Two methods of dexamethasone delivery were evaluated: elution from an electrode array alone, and elution from a cochlear implant electrode array in combination with a pre-operative systemic injection. All electrode arrays were implanted for a period of 4 weeks. Outcome measures at 4 weeks post-implantation included auditory brainstem response (ABR) thresholds, histological analysis of spiral ganglion neuron density, fibrotic tissue, new bone growth, and cochlear damage.

Results: Animals exposed to high surgical trauma showed greater hearing loss than those in the low trauma model, irrespective of the presence of dexamethasone. Whilst the area of intra-cochlear fibrotic tissue growth post-implantation was also independent of dexamethasone administration, new bone growth was significantly reduced in its presence. Our high trauma model effectively obliterated the organ of Corti and significantly reduced spiral ganglion neuron densities in the lower basal turn. This trauma-induced reduction in spiral ganglion neuron survival decreased with the inclusion of a dexamethasone-eluting array. A pre-operative systemic injection of dexamethasone did not significantly improve any outcome measures beyond those provided with a dexamethasone-eluting array alone.

Conclusion: Dexamethasone-eluting intra-cochlear arrays may inhibit osteoneogenesis, and reduce spiral ganglion neuron loss following traumatic cochlear implantation.

Keywords:

• Cochlear implant
• Dexamethasone
• Electrode insertion trauma
• Fibrous tissue growth
• Bone growth
• Corticosteroid
• Eluting electrode array

Acknowledgements

The authors acknowledge the financial support of the HEARing CRC, established under the Australian Government’s Cooperative Research Centres (CRC) Program. The CRC Program supports industry-led collaborations between industry, researchers and the community. We wish to thank Dr Sue Pierce for veterinary advice, Ms Prudence Nielsen for histological advice and assistance, and Drs Hayden Eastwood, Phillip Sale and David Rowe for their insightful discussions, and for advice and assistance using Amira 3D software. We also gratefully acknowledge Assoc Prof David Schramm for his useful comments in the review stage of this paper.

Notes on contributors

Scott Chambers is a Senior Research Assistant with close to a decade of experience in cochlear implant research. Scott has now extended his reach to research management.

Carrie Newbold was the Project Leader for this work, and other studies at the HEARing Cooperative Research Centre in Melbourne, Australia. Carrie now provides research consultation.

Dimitra Stathopoulos is a Senior Research Assistant at the HEARing Cooperative Research Centre. Dimitra began her work in cochlear implant research in 2002 and has been building her exceptional surgical and animal husbandry skills ever since.

Dr Karina Needham is head of the Hearing Neurosciences laboratory and a Senior Research Fellow at the University of Melbourne. Karina is now also the Project Leader at the HEARing Cooperative Research Centre. Her research interests and publications span the fields of neurophysiology, ion channels, optical neural stimulation, auditory physiology, stem cells, cochlear implants and hearing preservation strategies.

Chris Miller is an experienced technical program & project manager responsible for the timely development of highly engineered systems. Chris has expertly managed projects at Toyota, Cochlear Ltd, and now Tesla.

Frank Risi is the Global Group Product Manager, Surgical & Implants at Cochlear Ltd. Frank has over 17 years’ experience in the field of cochlear implants, with 15 years in implant research and development. Frank led Cochlear’s electrode developments for over 10 years and was responsible for the development of Cochlear’s commercial electrode portfolio as well as many research and clinical study devices.

Ya Lang Enke is currently a Senior Research Engineer within the Biosciences Group. Ya Lang has held a variety of technical and engineering roles at Cochlear Ltd since 2000.

Godofredo Timbol has been the lead device technician at Cochlear Ltd for close to two decades. Godofredo works closely with design engineers and other device technicians to develop new electrode arrays and implantable devices.

Prof Robert Cowan is CEO of the HEARing Cooperative Research Centre, a Principal Research Fellow at the University of Melbourne and an Adjunct Professor at Macquarie University. Bob’s research includes cochlear implant and hearing technology, audiology and biomedical research management.

Disclaimer statements

Contributors SC, CN, DS, CM, FR, YLE, GT and RC: concept and design of experiments. SC, CN and DS: acquisition of data. SC, CN, DS and KN: analysis and interpretation of data. SC, CN, DS, RC and KN: manuscript preparation and critical revision of article for content and accuracy.

Funding We acknowledge the financial support of the HEARing CRC, established and supported under the Cooperative Research Centres Program, an Australian Government initiative.

Conflicts of interest None.

Ethics approval This study was approved by the Animal Research and Ethics Committee of the Royal Victorian Eye and Ear Hospital.