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

Abstract

Cochlear implants (CIs) are auditory prostheses which replace the function of damaged sensory cells in the cochlea. Despite the success of CIs, our evidence shows some individuals have sub-optimal improvement in hearing function. We hypothesise that one source of variability arises from the priming of microglia and macrophages in response to inflammatory insults. Priming describes a change whereby microglia and macrophages exhibit an exaggerated inflammatory response to a second stimulus having previously been exposed to an initial ‘trigger’ stimulus. We will investigate whether a primary insult likely experienced by CI patients (noise exposure), causes priming. The presence and immunoreactivity of inflammatory markers will be measured from tissue collected from the cochlea and central auditory pathway of noise-exposed and control (sham-exposed) CBA mice, that we have auditory brainstem recordings (ABR) from. Whether priming leads to a heightened inflammatory response upon a secondary insult (cochlear implantation) will be determined by measuring cytokine production. This altered immune response could lead to the less favourable outcomes seen in CI users. Understanding whether microglia and macrophages become primed after initial insults and the effect on the subsequent inflammatory response, will contribute to determining whether robust control of inflammation will improve hearing outcomes after CI.

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Identifiers

ORCID for Katie Hough: orcid.org/0000-0002-5160-2517

ORCID for T. A. Newman: orcid.org/0000-0002-3727-9258

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