The immune response to cochlear implantation
Lead Research Organisation:
University of Southampton
Department Name: Faculty of Engineering & the Environment
Abstract
Hearing loss is a significant social, emotional and economic burden on society which affects around 466 million people worldwide and is expected to increase dramatically. Many people experience hearing loss due to loss of, or damaged hair cells in the cochlea, as it loses its ability to convert mechanical energy from sound waves into neural impulses due to these damaged sensory hair cells. Cochlear implants (CI) are auditory prostheses which function to bypass damaged hair cells and directly stimulate neurons of the auditory nerve which sends sound information directly to the brain, where the sound is perceived. Despite being the most utilised and successful neuroprosthetic device currently available, there are a group of individuals who have sub-optimal performance with their implants. The aim of this project is to investigate why these individuals experience sub-optimal performance with their implants and why this only
occurs in certain people. We hypothesise that one source of variability is the behaviour of the innate immune cells in responding to inflammatory insults. Resident macrophages and microglia may become primed, or have been primed due to immune events that were associated with the loss of hearing,which describes a change in their phenotype whereby these cells can exhibit an exaggerated inflammatory response to secondary stimulus, after experiencing a primary stimulus. This project will investigate whether a primary insult such as noise exposure, that results in altered hearing thresholds,causes microglial priming which would result in a heightened inflammatory response upon a secondary stimulus, in this case is cochlear implantation, leading to less favourable outcomes in cochlear implant patients. Immunohistochemistry will be carried out to identify the phenotype and regional distribution microglial cells and macrophages, in
cochlear and brain tissue, from CBA mice after a cochlear insult and to see how this changes with time and subsequent insult. We anticipate seeing changes in the regional distribution of microglia and macrophages and the activation of these cells in response to a cochlear insult resulting in an increased inflammatory response upon a secondary insult. Understanding the behaviour of microglia and macrophages in the cochlea and auditory pathway after an insult and subsequent insults and determining whether priming leads to an exaggerated inflammatory response, will be hugely beneficial in terms of considering the inflammatory status of an individual and how this will influence their outcomes with their cochlear implant
occurs in certain people. We hypothesise that one source of variability is the behaviour of the innate immune cells in responding to inflammatory insults. Resident macrophages and microglia may become primed, or have been primed due to immune events that were associated with the loss of hearing,which describes a change in their phenotype whereby these cells can exhibit an exaggerated inflammatory response to secondary stimulus, after experiencing a primary stimulus. This project will investigate whether a primary insult such as noise exposure, that results in altered hearing thresholds,causes microglial priming which would result in a heightened inflammatory response upon a secondary stimulus, in this case is cochlear implantation, leading to less favourable outcomes in cochlear implant patients. Immunohistochemistry will be carried out to identify the phenotype and regional distribution microglial cells and macrophages, in
cochlear and brain tissue, from CBA mice after a cochlear insult and to see how this changes with time and subsequent insult. We anticipate seeing changes in the regional distribution of microglia and macrophages and the activation of these cells in response to a cochlear insult resulting in an increased inflammatory response upon a secondary insult. Understanding the behaviour of microglia and macrophages in the cochlea and auditory pathway after an insult and subsequent insults and determining whether priming leads to an exaggerated inflammatory response, will be hugely beneficial in terms of considering the inflammatory status of an individual and how this will influence their outcomes with their cochlear implant
Organisations
People |
ORCID iD |
| Katie Hough (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509747/1 | 01/10/2016 | 30/09/2021 | |||
| 1938529 | Studentship | EP/N509747/1 | 25/09/2017 | 24/09/2020 | Katie Hough |
| Description | Analysed and characterised the cellular and tissue response in the fibrotic tissue that formed around a cochlear implant in a human. The first case of analysis of human tissue associated with an explanted CI from a living patient - with detailed clinical findings that provide evidence of progressive migration of the electrode array. - Characterised the cellular indicators of inflammation and fibrosis on an explanted human cochlear implant - Developed a pipeline for further analysis is human explant cases Investigating the biological response to cochlear implantation using a cochlear implant mouse model - Established a mouse model for cochlear implantation using electrode arrays which have been designed and optimised by Oticon. - Established methods to investigate the biological tissue response to the array including immunohistochemistry with an array of immune cells specific antibodies Characterising the immune profile of a mouse model for Otitis media (Junbo mouse model) as a model for investigation the effects of chronic inflammation on the auditory system. - Characterised the innate immune cell expression and morphology in Junbo mouse with and without the addition of an bacterial insult. |
| Exploitation Route | Developed a pipeline for tissue processing and analysis to analyse human fibrotic tissue from explanted cochlear implant cases Mouse model for cochlear implantation to further investigate: - The variable biological response at the tissue-electrode interface - The effects of acute and chronic stimulation with different parameters on the tissue response and to neural activity in the auditory pathway - The effects of different lifestyle factors on the biological response to the CI such as age, chronic inflammation/ infection, obesity Characterised a mouse model for otitis media which can be used to investigate the effects of inflammatory insults on the auditory system - relevance for age related hearing loss and dementia. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Alzheimer's Research UK South Coast Public Outreach Event |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Presented at a stand about the importance of hearing, hearing loss and links to dementia at an Alzheimer's public event - speaking to family members of people with dementia or even people with dementia. Discussing the links between lifestyle, hearing loss and dementia. And to remind people to get their hearing tested. |
| Year(s) Of Engagement Activity | 2018,2020 |