Exploring the Acute Effects of Glucocorticoids on Rabbit Vocal Fold Tissue

• Main Author: Gartling, Gary Joseph
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01.01.2021
• Subjects: Adenosine triphosphate; Kinases; Pharmacology; Physiology; Tumor necrosis factor-TNF; Vascular endothelial growth factor
• ISBN: 9798426865280

Glucocorticoids (GCs) are frequently used to treat vocal fold (VF) inflammation due to their potent anti-inflammatory effects. Glucocorticoids have varying pharmacodynamic properties with effects ranging from reduced angiogenesis, changes in epithelial/endothelial barrier integrity, reduced therapeutic effect after long-term use, and skeletal muscle atrophy. Despite the known diversity of drug activity and associated negative effects, otolaryngologists typically rely on subjective clinical judgments when prescribing GCs, rather than objective evidence of differential efficacy. Elucidating GC-induced VF tissue changes and delineating effects between GCs is necessary for physicians to accurately modify drug selection for patient-specific needs. To inform these knowledge gaps, in-vivo animal models are frequently used due to the ability to study experimentally induced tissue changes that would be impossible to conduct in humans. However, knowledge of the existence and localization of key VF constituents involved in the regulation of VF homeostasis in rabbits - a commonly used model in this field - has not yet been investigated.The purpose of this study was to: 1) Compare the localization of integral membrane proteins involved in the regulation of VF tissue homeostasis between human and rabbit VF tissue. 2) Investigate the acute effects of intramuscular injections of dexamethasone and methylprednisolone on VF tight junctions, vascularity, therapeutic efficacy, and thyroarytenoid (TA) muscle morphology in rabbit VFs. 3) Investigate the effects of an intracordal injection of dexamethasone on atrophy-associated gene expression and TA muscle morphology in rabbit VFs.The results of these experiments revealed: 1) Similar localization of key ion transport channels and cell adhesion proteins between rabbit and human VFs. 2) Increases in VF epithelial and endothelial tight junction expression in rabbits treated with 6-daily intramuscular injections of dexamethasone and decreases in global body mass in rabbits treated with methylprednisolone. 3) No evidence of GC-induced atrophy in the VFs of rabbits receiving an intracordal injection of dexamethasone. These findings provide support for the use of rabbits as an experimental model when studying key VF constituents, and evidence of differential effects of GCs at a systemic and VF level. These findings identify an important role for tailored GC selection dependent on patient-specific needs when treating voice disorders.