# Role of Macrophages on Tissue Remodeling Following Cochlear Implantation

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $209,579

## Abstract

Project Summary/Abstract
Hearing loss is a significant risk factor for dementia, including the most common form of CNS degenerative
disorder, Alzheimer’s disease (AD). Despite strong association, the cause-effect relationship between auditory
dysfunction and AD is unknown. Moreover, AD pathology can potentially affect the outcome of a cochlear
implant (CI), an auditory prosthesis that provides rehabilitation for patients with the most severe forms of
hearing loss. Based on preliminary data from CI patients and mouse models of AD, we hypothesize that the
neuropathological processes, including inflammation, that lead to CNS neurodegeneration in AD also impact
the response of the auditory nerve to acoustic and electrical stimulation. To test this hypothesis, Aim 1 uses a
CI system we recently developed to provide long-term electrical stimulation in mice to characterize the
electrophysiological function of the cochlea and auditory nerve in a mouse models of AD (5XFAD and AppNL-G-
F) after cochlear implantation. In a second aim we explore the hypothesize that the heighten neural
inflammatory state of AD mouse models will exacerbate inflammation and fibrosis in the cochlea following CI.
Hair cell counts, spiral ganglion neuron survival, and macrophage infiltration to the scala tympani, lateral wall
and spiral ganglia will be quantified. Fibrosis and neo-ossification in the scala tympani will be quantified using
3D X-ray microscopy and confirmed by -smooth muscle actin immunoreactivity. Taken together, these
studies will rigorously establish the electrophysiological and histopathological consequences of AD-related
neuropathologies on the auditory nerve and its ability to respond to electrical stimulation. Future studies will
expand the findings from this work to other mouse models of AD and will also explore these findings in our
large cohort of human CI recipients.

## Key facts

- **NIH application ID:** 10497996
- **Project number:** 3R01DC018488-02S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Marlan R Hansen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $209,579
- **Award type:** 3
- **Project period:** 2020-07-03 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10497996

## Citation

> US National Institutes of Health, RePORTER application 10497996, Role of Macrophages on Tissue Remodeling Following Cochlear Implantation (3R01DC018488-02S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10497996. Licensed CC0.

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