Chronic cochlear implantation with and without electric stimulation in a mouse model induces robust cochlear influx of CX3CR1+/GFP macrophages

Claussen, Alexander D.; Quevedo, Rene Vielman; Kirk, Jonathon; Higgins, Timon; Mostaert, Brian; Rahman, Muhammad Taifur; Oleson, Jacob; Hernandez, Reyna; Hirose, Keiko; Hansen, Marlan R.

doi:10.1016/j.heares.2022.108510

Cited by 17 publications

(21 citation statements)

References 56 publications

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“…In addition, in guinea pig cochlea, chronic ES at high charge densities evoked a vigorous tissue response and increased Pt electrode dissolution compared with Pt electrodes only 39 . Conversely, it has been reported that electric stimulation does not cause CX3CR1 + macrophages to migrate into the mouse cochlea 40 . Our in vitro results showed that electric stimulation did not induce migration and promoted the activity of macrophage and fibroblasts in the absence of inflammatory factors (Figures 2–5).…”

Section: Discussionmentioning

confidence: 49%

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Zhang,

Chen,

Wang

et al. 2023

Laryngoscope Investig Oto

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ObjectivesThe implanted electrodes deliver electric signals to spiral ganglion neurons, conferring restored hearing of cochlear implantation (CI) recipients. Postimplantation intracochlear fibrosis, which is observed in most CI recipients, disturbs the electrical signals and impairs the long‐term outcome of CI. The macrophages and fibroblasts activation is critical for the development of intracochlear fibrosis. However, the effect of electric stimulation of cochlear implant (ESCI) on the activity of macrophages and fibroblasts was unclear. In the present study, a human cochlear implant was modified to stimulate cultured macrophages and fibroblasts.MethodsBy measuring cellular marker and the expression level of cytokine production, the polarization and activity of macrophages and fibroblasts were examined with or without ESCI.ResultsOur data showed that ESCI had little effects on the morphology, density, and distribution of culturing macrophages and fibroblasts. Furthermore, ESCI alone did not affect the polarization of macrophages or the function of fibroblasts without the treatment of inflammatory factors. However, in the presence of LPS or IL‐4, ESCI further promoted the polarization of macrophages, and increased the expression of pro‐inflammatory or anti‐inflammatory factors, respectively. For fibroblasts, ESCI further increased the collagen I synthesis induced by TGF‐β1 treatment. Nifedipine inhibited ESCI induced calcium influx, and hereby abolished the promoted polarization and activation of macrophages and fibroblasts.ConclusionOur results suggest that acute inflammation should be well inhibited before the activation of cochlear implants to control the postoperative intracochlear fibrosis. The voltage‐gated calcium channels could be considered as the targets for reducing postimplantation inflammation and fibrosis.Level of EvidenceNA.

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Section: Discussionmentioning

confidence: 49%

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Zhang,

Chen,

Wang

et al. 2023

Laryngoscope Investig Oto

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“…Animal models are well established in CI research and have benefits as models in replicating the complex structure of the cochlea and its constituent tissues. By conducting in vivo experiments, it is possible to use the features of intact myelinated primary auditory neurons/ spiral ganglion neurons within the cochlea, an immunological response which is important in understanding chronic issues such as fibrosis and ossification [25,26,131], and potential for conducting some behavioural studies and measuring electrically evoked potentials [35,46,50,80] to conduct a wide range of CI studies to understand the CI-nerve interface.…”

Section: Animal Modelsmentioning

confidence: 99%

Models of Cochlea Used in Cochlear Implant Research: A Review

et al. 2023

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As the first clinically translated machine-neural interface, cochlear implants (CI) have demonstrated much success in providing hearing to those with severe to profound hearing loss. Despite their clinical effectiveness, key drawbacks such as hearing damage, partly from insertion forces that arise during implantation, and current spread, which limits focussing ability, prevent wider CI eligibility. In this review, we provide an overview of the anatomical and physical properties of the cochlea as a resource to aid the development of accurate models to improve future CI treatments. We highlight the advancements in the development of various physical, animal, tissue engineering, and computational models of the cochlea and the need for such models, challenges in their use, and a perspective on their future directions.

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“…CX3CR1, as a receptor for the chemokine Fractalkine, is found to express in NK cells, macrophages, monocytes, microglia, and partly T cells ( Jung et al, 2000 ). CX3CR1 is also expressed in macrophages and monocytes of the mouse cochlea ( Claussen et al, 2022 ). In response to the transformation of monocytes and migration of macrophages in hearing damage caused by noise stimulation ( Shin et al, 2022a , b ), CX3CR1 regulates the inflammatory response caused by cochlear injury ( Zhang et al, 2021 ).…”

Section: Roles Of Class a G Protein-coupled Receptors In Cochleamentioning

confidence: 99%

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

Guo²,

Fu³

et al. 2022

Front. Mol. Neurosci.

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The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient’s hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.

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Chronic cochlear implantation with and without electric stimulation in a mouse model induces robust cochlear influx of CX3CR1+/GFP macrophages

Cited by 17 publications

References 56 publications

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Electrical stimulation of cochlear implant promotes activation of macrophages and fibroblasts under inflammation

Models of Cochlea Used in Cochlear Implant Research: A Review

G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss

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