A comparative study of intratympanic steroid and NO synthase inhibitor for treatment of cochlear lateral wall damage due to acute otitis media.

We studied the damage to the cochlear lateral wall induced by otitis media and the therapeutic effects of intratympanic administration of steroid and nitric oxide (NO) synthase inhibitor. In Sprague-Dawley rats, right middle ear cavities were inoculated with lipopolysaccharide, followed after 30 min by intratympanic administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler flowmetry. Prostaglandin E(1) was topically applied to the round window membrane of the right ear and changes in cochlear blood flow were calculated. Changes of cochlear blood flow were significantly different among the three groups. Increases in cochlear blood flow following PGE(1) application were higher in the group that received NOS-inhibitor. Electron microscopic examination revealed that changes in the stria vascularis were less severe in rats treated with dexamethasone or NOS-inhibitor. Our results show the effectiveness of intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall damage caused by otitis media.

Matrix metalloproteinases in a gerbil cholesteatoma model.

OBJECTIVE: The goal of this study was to determine whether expression of matrix metalloproteinases (MMP) and tumor necrosis factor-alpha (TNF-alpha) occurs in a gerbil cholesteatoma model, which may be involved early in the pathogenesis of cholesteatoma. Study design Atelectasis was induced by transpalatal, bilateral Eustachian tube obstruction on gerbil ears (n = 60). Tympanic membranes were removed at days 0, 3, 7, 14, 28, 56, and 84, and quantitative analysis of TNF-alpha and MMPs was performed. RESULTS: Atelectasis and middle ear inflammation increased with time. TNF-alpha and MMP levels increased (P < 0.0083) with time, inflammation, and atelectatic stage with some variability seen between different MMPs. CONCLUSION: Elevation of TNF-alpha and MMPs associated with progressive tympanic membrane atelectasis suggests a possible role for these inflammatory mediators in the pathogenesis of cholesteatoma.

An immunohistochemical study of inducible nitric oxide synthase in the rat middle ear, with reference to tympanosclerosis.

Tympanosclerosis and myringosclerosis are well-known sequelae after acute and chronic otitis media and are also often seen after treatment of secretory otitis media with ventilation tubes. They sometimes cause serious hearing disability. There is no successful treatment for these conditions. There might be factors triggering an immunological or autoimmune chain reaction, which leads to tympanosclerosis. Intervention with the aim of abolishing this type of response might be possible if an interruption of the chain reaction can be found. Nitric oxide is a radical molecule with the ability to kill pathogens and is produced by the enzyme nitric oxide synthase. Expression of inducible nitric oxide synthase (iNOS) was analysed immunohistochemically in a rat model of acute otitis media. In rats sacrificed at days 3 and 6 after inoculation. iNOS was also strongly expressed in the middle ear mucosa and in the tympanic membrane as well as in the inner ear. In control specimens as well as in infected ones. iNOS was expressed in the tissue of the external ear canal. In rats sacrificed at day 10 and after 3 months, iNOS was expressed at the same locations, although less frequently. These data indicate that iNOS expression is induced during acute otitis media and suggest that nitric oxide may be important in the host defence against ear infections.

Quantitative immunogold localization of Na+,K(+)-ATPase alpha-subunit in the tympanic wall of rat cochlear duct.

Ultrastructural localization of Na+,K(+)-ATPase was quantitatively investigated in the tympanic wall of rat cochlear duct by use of the protein A-gold method, using an affinity-purified antibody against the alpha-subunit of rat kidney Na+,K(+)-ATPase. A moderate number of gold particles were found on the basolateral membrane of the interdental cells of the spiral limbus. A small number of gold particles were found on the basolateral surfaces of the border cells and Hensen's cells. On the inner and outer sensory hair cells, however, the plasma membranes were rarely labeled by gold particles. The general pattern of labeling densities in cochlear structures determined here and in a previous communication from our laboratory shows good correlation with the distribution of Na+,K(+)-ATPase activity as previously estimated biochemically, cytochemically, and autoradiographically.