Objectives/HypothesisGlucocorticoids (GC)s are commonly employed to treat vocal fold (VF) pathologies. However, VF atrophy has been associated with intracordal GC injections. Dexamethasone‐induced skeletal muscle atrophy is well‐documented in other tissues and believed to be mediated by increased muscle proteolysis via upregulation of Muscle Ring Finger (MuRF)‐1 and Atrogin‐1. Mechanisms of dexamethasone‐mediated VF atrophy have not been described. This pilot study employed in vitro and in vivo models to investigate the effects of dexamethasone on VF epithelium, thyroarytenoid (TA) muscle, and TA‐derived myoblasts. We hypothesized that dexamethasone will increase atrophy‐associated gene expression in TA muscle and myoblasts and decrease TA muscle fiber size and epithelial thickness.Study DesignIn vitro, pre‐clinical.MethodsTA myoblasts were isolated from a female Sprague–Dawley rat and treated with 1 μM dexamethasone for 24‐h. In vivo, 15 New Zealand white rabbits were randomly assigned to three treatment groups: (1) bilateral intracordal injection of 40 μL dexamethasone (10 mg/ml; n = 5), (2) volume‐matched saline (n = 5), and (3) untreated controls (n = 5). Larynges were harvested 7‐days post‐injection. Across in vivo and in vitro experimentation, MuRF‐1 and Atrogin‐1 mRNA expression were measured via RT‐qPCR. TA muscle fiber cross‐sectional area (CSA) and epithelial thickness were also quantified in vivo.ResultsDexamethasone increased MuRF‐1 gene expression in TA myoblasts. Dexamethasone injection, however, did not alter atrophy‐associated gene expression, TA CSA, or epithelial thickness in vivo.ConclusionDexamethasone increased atrogene expression in TA myoblasts, providing foundational insight into GC induced atrophic gene transcription. Repeated dexamethasone injections may be required to elicit atrophy in vivo.Level of EvidenceNA Laryngoscope, 133:2264–2270, 2023

Objectives Functional outcomes following microflap surgery for vocal fold pathology are favorable. Although the stratified squamous epithelium appears to heal rapidly, persistent physiologic tissue alterations are likely. We sought to elucidate key biochemical processes including recruitment of immune cells, regulation of cellular junction proteins, and long‐term alterations to epithelial tissue permeability following microflap with an eye toward enhanced clinical outcomes. Methods Forty New Zealand rabbits were assigned to eight groups (n = 5/group): no‐injury control or bilateral microflap with survival for 0 h, 12 h, 1 day, 3 days, 7 days, 30 days, and 60 days post‐microflap. The epithelium was dissected from one vocal fold and transepithelial resistance was quantified. The contralateral fold was subjected to transmission electron microscopy. Images were evaluated by a blinded rater and paracellular space dilation was quantified using ImageJ. Immune cell infiltration was evaluated and recorded qualitatively. Results Increased innate immune response was observed 12 h as well as 7 and 30 days after microflap. At 60 days following injury, decreased epithelial resistance was observed. Paracellular spaces were dilated at all time‐points following injury. Conclusions The vocal fold epithelium was significantly altered at 60 days following microflap. The implications for this tissue phenotype are unclear. However, compromised epithelial barrier function is implicated in various diseases and may increase the risk of subsequent injury. Level of Evidence NA Laryngoscope, 133:350–356, 2023

Objectives/Hypothesis: Systemic glucocorticoids (GC)s are employed to treat various voice disorders. However, GCs have varying pharmacodynamic properties with adverse effects ranging from changes in epithelial integrity, skeletal muscle catabolism, and altered body weight. We sought to characterize the acute temporal effects of systemic dexamethasone and methylprednisolone on vocal fold (VF) epithelial glucocorticoid receptor (GR) nuclear translocation, epithelial tight junction (ZO-1) expression, thyroarytenoid (TA) muscle fiber morphology, and body weight using an established pre-clinical model. We hypothesized dexamethasone and methylprednisolone will elicit changes in VF epithelial GR nuclear translocation, epithelial ZO-1 expression, TA muscle morphology, and body weight compared to placebo-treated controls. Methods: Forty-five New Zealand white rabbits received intramuscular injections of methylprednisolone (4.5 mg; n = 15), dexamethasone (450 µg; n = 15), or volume matched saline ( n = 15) into the iliocostalis/longissimus muscle for 6 consecutive days. Vocal folds from 5 rabbits from each treatment group were harvested at 1-, 3-, or 7 days following the final injection and subjected to immunohistochemistry for ZO-1 and GR as well as TA muscle fiber cross-sectional area (CSA) measures. Results: Dexamethasone increased epithelial GR nuclear translocation and ZO-1 expression 1-day following injections compared to methylprednisolone ( P = .024; P = .012). Dexamethasone and methylprednisolone increased TA CSA 1-day following injections ( P = .011). Methylprednisolone decreased body weight 7 days following injections compared to controls ( P = .004). Conclusions: Systemic dexamethasone may more efficiently activate GR in the VF epithelium with a lower risk of body weight loss, suggesting a role for more refined approaches to GC selection for laryngeal pathology.