title: Influence of continuous negative pressure in the rat middle ear.
abstract: OBJECTIVE
  High negative pressure in the middle ear was thought to be closely related to the etiology of retraction-type cholesteatoma. Recently, it has been detected that mechanical forces are important factors in epithelial turnover and affect cytoskeletal remodeling. Continuous negative pressure in the middle ear may possibly accelerate the proliferation and differentiation of epithelial cells of the tympanic membrane.
  
  
  METHODS
  Animal experimental study.
  
  
  METHODS
  Eleven adult male Sprague-Dawley rats were used, and continuous negative pressure was loaded by connecting a catheter from the rat's middle ear to the supply route of an implantable microinfusion pump, iPRECIO. At 7 days after implantation of the device, an otoendoscopic examination and micro-computed tomography (CT) analysis of the temporal bone were performed; the temporal bones were then collected for histological and immunohistochemical analysis. The degree of proliferation and differentiation of epithelial cells of the tympanic membrane was investigated immunohistochemically using the anti-cytokeratin-5 and anti-cytokeratin-10 antibodies.
  
  
  RESULTS
  Otoendoscopic examination revealed retraction of the pars flaccida in all of the ears under negative pressure. In the micro-CT analysis, soft tissue density area in the hypotympanum was observed in all ears under negative pressure. Histological analysis revealed thickened epithelium of the pars flaccida. In this region, the thickness of layers with cytokeratin-5-positive cells and cytokeratin-10-positive cells were increased.
  
  
  CONCLUSIONS
  Continuous negative pressure in the middle ear can lead to thickening of the epithelium of the pars flaccida, and may accelerate the proliferation and differentiation of epithelial cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Naotaro
authors.initials: N
authors.lastname: Akiyama
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yamamoto-Fukuda
authors.forename: Haruo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002781:Cholesteatoma / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000503:physiopathology*; D004724:Endoscopy; D004847:Epithelial Cells / Q000473:pathology; D008297:Male; D038781:Otoscopy; D011312:Pressure / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018058:Tympanic Membrane Perforation / Q000209:etiology* / Q000473:pathology; D055114:X-Ray Microtomography
keywords: Negative pressure; cell proliferation and differentiation.; cholesteatoma; middle ear; pars flaccida