Vocal fold injury models in rats: a literature review on techniques and methodology

Abstract

This study reviewed the current literature on technical aspects regarding controlled vocal fold injuries in the rat model. Data from PubMed, Embase, and Scopus database for English language literature was collected to identify methodological steps leading to a controlled surgical injury of the rat vocal fold. Inclusion criteria: full disclosure of anesthesia protocol, positioning of the rat for surgery, vocal fold visualization method, instrumentation for vocal fold injury, vocal fold injury type. Articles with partial contribution were evaluated and separately included due to the limited number of original methodologies. 724 articles were screened, and eleven articles were included in the analysis. Anesthesia: ketamine hydrochloride and xylazine hydrochloride varied in dose from 45 mg/kg and 4.5 mg/kg to 100 mg/kg and 10 mg/kg. Visualization: The preferred method was the 1.9 mm, 25-30 degree endoscopes. The widest diameter endoscope used was 2.7 mm with a 0 or 30 degree angle of view. Instruments for lesion induction range from 18 to 31G needles, microscissors, micro forceps to potassium titanyl phosphate, and blue light lasers. Injury types: vocal fold stripping was the main injury type, followed by vocal fold scarring and charring. One article describes scaffold implantation with injury to the superior aspect of the vocal fold. Rats are good candidates for in vivo larynx and vocal folds research. A more standardized approach should be considered regarding the type of vocal fold injury to ease data comparison.

Keywords: injury; methodology; rat; review; vocal fold.

Figure 1.

Histological layers of the normal rat vocal fold. The three layers of the rat vocal fold; 200x magnification with HE staining. VF – vocal fold; ECM – extra cellular matrix.

Figure 2.

Macroscopic anatomy of the rat vocal fold and surrounding region. A: V – vallecular; E – epiglottis; SP – soft palate; Ar – Left arytenoid cartilage. B: The right membranous the vocal is marked with a white arrow and can be found inferior to the base of the epiglottis. The arytenoid is marked with the red arrow. These are important landmarks helping to identify the true membranous vocal folds.

Figure 3.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) flowchart summarizing the search results and the application of eligibility criteria.