Recovery of Vocal Fold Epithelium after Acute Phonotrauma

Abstract

We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions.

In vitro mechanical vibration down-regulates pro-inflammatory and pro-fibrotic signaling in human vocal fold fibroblasts

“…In an in vivo rabbit model, Rousseau et al investigated wound healing processes after an acute phonotrauma, focusing on the epithelial layer of the VF. Again a significant upregulation of IL1β and TGF-β1 was revealed after 120 minutes of phonatory stress [59]. In line with these results, the upregulation of ECM-and inflammation-related genes and proteins in our experiments, such as collagen, HA as well as IL1β, TGF-β1 and IL6 reflect the applicability of our model, even though only one cell type was included.…”

The Therapeutic Effects of Straw Phonation on Vocal Fatigue

“…PTP, the lowest subglottal pressure to initiate and sustain stable vocal fold vibration, is associated with tissue viscoelasticity of vocal folds. The increase in PTP after a prolonged vocal loading and the decline in PTP during vocal recovery may be related to the vocal fold epithelial barrier integrity and function . Additionally, a more significant decrease in PTP was observed with the straw phonation condition when compared to the vocal rest condition; however, the mechanism behind the therapeutic effects of straw phonation on vocal fatigue is still unclear.…”

“…The increase in PTP after a prolonged vocal loading and the decline in PTP during vocal recovery may be related to the vocal fold epithelial barrier integrity and function. [36][37][38][39] Additionally, a more significant decrease in PTP was observed with the straw phonation condition when compared to the vocal rest condition; however, the mechanism behind the therapeutic effects of straw phonation on vocal fatigue is still unclear. We hypothesized that its effects could be attributed to two possible aspects.…”

Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx

“…In addition, epithelial injury can further accelerate cell turnover [ 26 ]. Accelerated epithelial turnover has been previously demonstrated following iatrogenic VF injury [ [92] , [93] , [94] ]. We hypothesize in order to escalate epithelial cell turnover, the glottic region increased cell proliferation at day 1 as an adaptive response to CS [ 29 ], and its tolerance may be critical to maintain and protect the VF from injury, at least in the short-term.…”