# Manipulating Macrophage Phenotype to Accelerate Recurrent Laryngeal Nerve Repair

> **NIH NIH R01** · CORNELL UNIVERSITY · 2022 · $392,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Vocal fold paralysis (VFP) occurs when the recurrent laryngeal nerve (RLN) is injured, most commonly during
surgery of the neck. Bilateral injury to the RLN can result in potentially life-threatening airway obstruction and
the need for tracheostomy. The RLN can regenerate some of its axons, but in many patients with paralysis some
form of intervention is required to correct the airway obstruction and voice changes. This is most frequently
achieved through reinnervation of the laryngeal muscles to restore function. Current practice is to wait 6-24
months before any intervention is performed as spontaneous recovery can occur. This delay before repair allows
chronic changes in the nerve distal to the site of injury to occur and results in poor recovery. The overall goal of
this proposal is to accelerate recovery after RLN injury and reduce the consequences of prolonged denervation
before nerve graft. Previous work has focused mainly on events that occur late in the repair and remodeling
process. Little is known about how manipulating events in the early stages of repair can be used to improve
recovery. We have recently shown that modifying the type of macrophages accumulating at the graft site early
after injury increases Schwann cell migration in the regenerative bridge and improves recovery.
Our preliminary data show that when graft is delayed the phenotype of macrophages at the repair site is altered.
We hypothesize that changes in the function of senescent Schwann cells (SC) in the distal nerve stump are
responsible for this change. In this proposal we will evaluate how macrophage and SC function and gene
expression are altered after delayed graft. We will determine gene expression, phagocytosis and migration for
both cell types and determine the consequences of these changes on tissue remodeling using a variety of
techniques including protein expression, the formation of a polarized microvasculature, axon extension and the
number of axons reaching their target.
Our preliminary data also demonstrate that an exogenous anti-inflammatory ligand can alter macrophage
phenotype and promote axon extension and the formation of neuromuscular junctions. We will then test the
neuroprotective ability of this ligand to rescue the changes we have identified in delayed repair and then confirm
these changes are mediated by macrophages. Finally, we test the ability of manipulation of macrophage
phenotype to accelerate recovery after acute injury using a translational animal model. The ability to accelerate
recovery following RLN injury, by intervening intra-operatively, would reduce the consequences of delayed repair
and improve recovery for patients with VFP.

## Key facts

- **NIH application ID:** 10434792
- **Project number:** 5R01DC017171-05
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Jonathan Cheetham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434792

## Citation

> US National Institutes of Health, RePORTER application 10434792, Manipulating Macrophage Phenotype to Accelerate Recurrent Laryngeal Nerve Repair (5R01DC017171-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434792. Licensed CC0.

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