Immunohistochemical Study of Cell Proliferation using BrdU Labelling on Tympanic Membrane, External Auditory Canal and Induced Cholesteatoma in Mongolian Gerbils

Abstract

The Mongolian gerbil is a well-known animal model for induction of aural cholesteatomas. This animal model is useful for studying changes in the keratinizing epithelium. It is not known whether keratin accumulation can increase the proliferative activity of the keratinizing epithelium in tympanic membrane and meatal skin. In this study, we investigated the proliferative activity of the epidermis in induced aural cholesteatoma at various stages and in different areas of the tympanic membrane and meatal skin in normal gerbils. Anti-5-bromo-2- deoxyuridine (BrdU) was injected intraperitoneally to detect the proliferative activity of keratinizing epithelium. Immunohistochemistry with monoclonal BrdU antibody in the normal gerbil showed intense immunolabelled keratinocytes at the handle of malleus, and the superior parts of pars tensa and pars flaccida. Also, mitotic activity in the deep meatal skin was more active than in the lateral meatal skin. The induced aural cholesteatoma showed more active proliferation centre of the epithelial cell than eardrum and external ear canal of the normal gerbil. These observations suggest that the accumulation of the keratin debris might induce changes of the cellular proliferation in the external auditory meatus.

Animal Models of Middle Ear Cholesteatoma

“…They indicated that the thickness of the fibrous layer was almost doubled, mostly because of an increased amount of collagen fibers, and the acoustic stiffness was significantly increased in all cholesteatoma ears. Park et al investigated the immunohistochemical study of cell proliferation using BrdU labeling [37] and the expression of PLG-gamma1, ligand-mediated signal transduction for cell proliferation [38] on the tympanic membrane, external auditory canal, and induced cholesteatoma in gerbils. According to the results, the induced aural cholesteatoma showed a more active proliferation center of the epithelial cell and more intense immunolabeling of PLG-gamma1 protein than the eardrum and external ear canal of the normal gerbil.…”

Cholesteatoma of the external auditory meatus

“…Наиболее часто встречается спонтанная ХНСП, причиной развития которой является снижение с возрастом (средний возраст наблюдаемых пациентов составил 43 года) нормальной миграционной способности эпидермиса наружного слухового прохода [6]. Кроме этого, ее образование связывают с нарушением клеточной пролиферации в условиях избыточного накопления слущенного эпидермиса [7].…”