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Investigating immune priming in the auditory system as a cause of variable outcomes after cochlear implantation

Investigating immune priming in the auditory system as a cause of variable outcomes after cochlear implantation
Investigating immune priming in the auditory system as a cause of variable outcomes after cochlear implantation
Aim
Despite the huge success of cochlear implants (CIs), our evidence shows some individuals have less favorable outcomes with their CI either immediately after implantation or in the subsequent years following surgery. We hypothesise that one source of variability arises from the priming of innate immune cells, in response to inflammatory insults. Priming describes a change whereby these cells exhibit an exaggerated inflammatory response to a second stimulus having previously been exposed to an initial ‘trigger’ stimulus. Using mouse models, we aim to investigate whether a primary insult likely experienced by CI patients such as noise-exposure or surgical insertion of the implant itself, causes priming of the innate immune cells; macrophages and microglia. Additionally, we will investigate whether the combination of pre-exposure to a primary insult and then cochlear implantation leads to a heightened inflammatory response upon this secondary insult; which could lead to the less favourable outcomes seen in CI users.

Method
Mice will be exposed to varying primary insults such a noise-exposure (octave band noise 8-16 kHz 100 dB SPL for 2 hours) and cochlear implantation (with CIs supplied by Oticon medical). Electrodes designed of different materials including pure silicon and platinum (+PEDOT and +PEDOT and dexamethasone) will be implanted into CBA mice to determine variation in the overall inflammation in the tissue surrounding the electrode. Any evidence of metal shedding from the electrode will also be investigated using immunostaining.

Tissue will be collected, processed and sectioned to enable immunohistochemical analysis after each primary insult, with the aim to measure and characterise the presence and phenotype of the innate immune cells in close proximity to the electrode and along the auditory pathway. Biomedical imaging will be used to support this.
We will then measure whether the addition of a secondary insult leads to an exaggerated inflammatory response by measuring cytokine production.


Results
In the noise-exposed mouse model, ABR recordings have shown an increase in threshold post-exposure compared to control, indicating functional damage to hearing function. Immunohistochemical staining has confirmed the presence and identified the morphology of microglia/macrophages in key regions of the cochlea and auditory pathway, suggesting these cells may experience a change in phenotype in response to an immune challenge such as implantation. The expression of genes involved in the activation and signalling of the cells will be measured by RNAscope to further characterise their phenotype

In the CI model, surgical technique and implant design are being continually optimised to ensure correct insertion and successful recovery of the mice. This will ensure sufficient time for the inflammatory response to occur before obtaining the tissue for analysis. CT scanning has provided detailed, structural 3D information about the cochlea pre-implantation and will be used as a method to validate our surgical technique post-implantation.

Conclusion
For CI users, life-long success with their implant is pivotal to enable the connection and communication with the world around them. Our group believes that the lifestyle choices we make and the impact this has on our immune system, could play a role in how individuals succeed with their CIs. Gaining a better understanding of the immune response to cochlear implantation in the auditory system through the use of mouse models, presents an opportunity to develop clinical biomarkers which could allow early identification of individuals with an increased inflammatory status. This would initiate the appropriate anti-inflammatory interventions to optimise CI performance. Additionally, it would support the optimisation of electrode design to ultimately improve long-term hearing performance and ensure positive patient outcomes for life.
Hough, Kate
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Sanderson, Alan Peter
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Anderson, Lucy
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Impey, Bethan
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Verschuur, Carl
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Newman, Tracey
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Hough, Kate
4ab6ce34-81be-4bff-bdc1-bdd22bbb0ace
Sanderson, Alan Peter
79d72ecf-7722-4a39-be5f-a041ba423c2b
Anderson, Lucy
efaa3028-3a49-4ad2-9a4b-9ca4f3ccf9c2
Impey, Bethan
3a24a18e-a0b3-425e-805f-5900a907d073
Verschuur, Carl
5e15ee1c-3a44-4dbe-ad43-ec3b50111e41
Newman, Tracey
322290cb-2e9c-445d-a047-00b1bea39a25

Hough, Kate, Sanderson, Alan Peter, Anderson, Lucy, Impey, Bethan, Verschuur, Carl and Newman, Tracey (2019) Investigating immune priming in the auditory system as a cause of variable outcomes after cochlear implantation. British Cochlear Implant Group Meeting. 04 - 05 Apr 2019.

Record type: Conference or Workshop Item (Poster)

Abstract

Aim
Despite the huge success of cochlear implants (CIs), our evidence shows some individuals have less favorable outcomes with their CI either immediately after implantation or in the subsequent years following surgery. We hypothesise that one source of variability arises from the priming of innate immune cells, in response to inflammatory insults. Priming describes a change whereby these cells exhibit an exaggerated inflammatory response to a second stimulus having previously been exposed to an initial ‘trigger’ stimulus. Using mouse models, we aim to investigate whether a primary insult likely experienced by CI patients such as noise-exposure or surgical insertion of the implant itself, causes priming of the innate immune cells; macrophages and microglia. Additionally, we will investigate whether the combination of pre-exposure to a primary insult and then cochlear implantation leads to a heightened inflammatory response upon this secondary insult; which could lead to the less favourable outcomes seen in CI users.

Method
Mice will be exposed to varying primary insults such a noise-exposure (octave band noise 8-16 kHz 100 dB SPL for 2 hours) and cochlear implantation (with CIs supplied by Oticon medical). Electrodes designed of different materials including pure silicon and platinum (+PEDOT and +PEDOT and dexamethasone) will be implanted into CBA mice to determine variation in the overall inflammation in the tissue surrounding the electrode. Any evidence of metal shedding from the electrode will also be investigated using immunostaining.

Tissue will be collected, processed and sectioned to enable immunohistochemical analysis after each primary insult, with the aim to measure and characterise the presence and phenotype of the innate immune cells in close proximity to the electrode and along the auditory pathway. Biomedical imaging will be used to support this.
We will then measure whether the addition of a secondary insult leads to an exaggerated inflammatory response by measuring cytokine production.


Results
In the noise-exposed mouse model, ABR recordings have shown an increase in threshold post-exposure compared to control, indicating functional damage to hearing function. Immunohistochemical staining has confirmed the presence and identified the morphology of microglia/macrophages in key regions of the cochlea and auditory pathway, suggesting these cells may experience a change in phenotype in response to an immune challenge such as implantation. The expression of genes involved in the activation and signalling of the cells will be measured by RNAscope to further characterise their phenotype

In the CI model, surgical technique and implant design are being continually optimised to ensure correct insertion and successful recovery of the mice. This will ensure sufficient time for the inflammatory response to occur before obtaining the tissue for analysis. CT scanning has provided detailed, structural 3D information about the cochlea pre-implantation and will be used as a method to validate our surgical technique post-implantation.

Conclusion
For CI users, life-long success with their implant is pivotal to enable the connection and communication with the world around them. Our group believes that the lifestyle choices we make and the impact this has on our immune system, could play a role in how individuals succeed with their CIs. Gaining a better understanding of the immune response to cochlear implantation in the auditory system through the use of mouse models, presents an opportunity to develop clinical biomarkers which could allow early identification of individuals with an increased inflammatory status. This would initiate the appropriate anti-inflammatory interventions to optimise CI performance. Additionally, it would support the optimisation of electrode design to ultimately improve long-term hearing performance and ensure positive patient outcomes for life.

Text
BCIG Poster -Kate Hough
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More information

Published date: 4 April 2019
Venue - Dates: British Cochlear Implant Group Meeting, 2019-04-04 - 2019-04-05

Identifiers

Local EPrints ID: 443687
URI: http://eprints.soton.ac.uk/id/eprint/443687
PURE UUID: a8cd1811-011f-424c-a343-bbb093ffb14c
ORCID for Kate Hough: ORCID iD orcid.org/0000-0002-5160-2517
ORCID for Tracey Newman: ORCID iD orcid.org/0000-0002-3727-9258

Catalogue record

Date deposited: 09 Sep 2020 16:30
Last modified: 18 Feb 2021 17:32

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Contributors

Author: Kate Hough ORCID iD
Author: Alan Peter Sanderson
Author: Lucy Anderson
Author: Bethan Impey
Author: Carl Verschuur
Author: Tracey Newman ORCID iD

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