Bacterial Cytolysin Perturbs Round Window Membrane Permeability Barrier In Vivo: Possible Cause of Sensorineural Hearing Loss in Acute Otitis Media

Engel, Frank; Blatz, R; Schliebs, Reinhard; Palmer, Michaël; Bhakdi, Sucharit

doi:10.1128/iai.66.1.343-346.1998

Cited by 23 publications

(8 citation statements)

References 27 publications

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“…This toxin may permeate an intact round window to manifest as hearing loss. 68 Endotoxin, a ubiquitous component of H influenzae and other Gram-negative bacilli, 64 may exert similar cochleotoxic effects. 71 Thus toxins common to all strains of S pneumoniae and H influenzae, and independent of overall virulence, could be responsible for the hearing loss observed in both the fenestrated and non-fenestrated ears.…”

Section: Discussionmentioning

confidence: 99%

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Hearing Preservation With Labyrinthine Ablation in Otitis Media

2000

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Objectives: Iatrogenic fenestration of the inner ear in the presence of otitis media is commonly associated with permanent hearing loss. Hearing can generally be preserved when the vestibular labyrinth is ablated in a controlled manner in noninflamed ears. The purpose of this study was to examine the feasibility of hearing preservation with violation of the inner ear in the presence of middle ear inflammation. Study Design: Prospective and controlled animal model. Methods: Otitis media was induced bilaterally in pigmented guinea pigs with transtympanic injection of Streptococcus pneumoniae, nontypeable Haemophilus influenzae, or formalin-killed nontypeable H influenzae. Two to 4 days after injection, the horizontal canal of one ear was transected and sealed. Hearing was tested before and after labyrinthine ablation. Results: Otitis media was induced in all ears. Bacterial cultures were positive in 19 of 20 S pneumoniaeinjected ears, and in 10 of 16 nontypeable H influenzae-injected ears. One week after surgery, elevation of click thresholds (> 15 dB) was encountered in none of the fenestrated or unfenestrated S pneumoniaeinfected ears, in two of six unfenestrated and three of six fenestrated nontypeable H influenzae-infected ears, and in one of five killed-nontypeable H influenzae-injected ears both with and without fenestration. Conclusions: These data suggest that ablation of a semicircular canal in the presence of middle ear inflammation or infection does not necessarily lead to profound sensorineural hearing loss. Hearing loss associated with iatrogenic violation of the semicircular canals may be more dependent on factors other than the presence of nonspecific middle ear inflammation.

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Section: Discussionmentioning

confidence: 99%

“…The cochleotoxic effects of S pneumoniae have been attributed primarily to the production of an exotoxin, pneumolysin. 65–68 Although this toxin does not appear to play a major role in overall virulence, 69,70 it is nearly universally produced by S pneumoniae . This toxin may permeate an intact round window to manifest as hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Hearing Preservation With Labyrinthine Ablation in Otitis Media

2000

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“…Presence of histamine, prostaglandins, leukotrienes and bacterial toxins can increase the permeability of RWM and subsequently the passage of substances from middle ear into the inner ear. On other hand deposition of inflammatory product on RWM reduces the permeability [44,45,49,55,78,82,[84][85][86].…”

Section: Variability Of the Outcomesmentioning

confidence: 99%

Use of the biodegradable polymer chitosan as a vehicle for applying drugs to the inner ear

Saber

Strand

Ulfendahl

2010

European Journal of Pharmaceutical Sciences

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“…and trimethylphenylammonium pass through the window.l'' whereas high-molecular weight compounds significantly penetrate only a round window damaged by noxious agents. 19 However, we think that diffusion was not the main route of NCT to the inner ear in our study. First, NCT as a sodium salt of an amino acid is more hydrophilic than the above-mentioned substances and will not penetrate the 3 layers of the round window easily.-?…”

Section: Discussionmentioning

confidence: 53%

Tolerability of N-Chlorotaurine in the Guinea Pig Middle Ear: A Pilot Study Using an Improved Application System

Neher¹,

Nagl²,

Prieskorn³

et al. 2004

Ann Otol Rhinol Laryngol

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The tissue tolerance of N-chlorotaurine (NCT), a mild endogenous antimicrobial oxidant, has been investigated by application to the guinea pig middle ear. The animals were implanted with a novel cannula system that allows chronic external drug delivery to the round window niche. In the first part of the study, 3 animals each received 100 microL of 0.1% NCT (5.5 mmol/L) and 1% NCT, respectively, in aqueous solution twice daily for 8 days. In the second part, NCT was dissolved in phosphate-buffered saline solution to 300 milliosmolar (isotonic), and 27 microL was injected in 3 additional animals twice daily for 7 days. The guinea pigs injected with 100 microL of NCT developed immediate dizziness and nystagmus and did not thrive. Other reactions included mucosal thickening in the middle ear, rupture of the tympanic membrane, and blood and gelatinous material in the cochlea accompanied by hair cell loss and a 10- to 90-dB elevation of the hearing threshold as determined by auditory brain stem responses. The effects seemed to be dose-dependent, but the rate of variability was high across animals. In contrast, the guinea pigs treated with 27 microL of isotonic NCT showed no signs of discomfort, no or only moderate thickening of the middle ear mucosa, no shift of the hearing threshold, and no hair cell loss. Positive control animals injected with 10% neomycin sulfate developed extensive hair cell loss. Provided that the membranes of the inner ear are intact and that low single-dose volumes are used to avoid increased middle ear pressure, isotonic NCT seems to be well tolerated in the tympanic cavity. The new drug delivery system proved to be advantageous for ototoxicity studies.

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Bacterial Cytolysin Perturbs Round Window Membrane Permeability Barrier In Vivo: Possible Cause of Sensorineural Hearing Loss in Acute Otitis Media

Cited by 23 publications

References 27 publications

Hearing Preservation With Labyrinthine Ablation in Otitis Media

Hearing Preservation With Labyrinthine Ablation in Otitis Media

Use of the biodegradable polymer chitosan as a vehicle for applying drugs to the inner ear

Tolerability of N-Chlorotaurine in the Guinea Pig Middle Ear: A Pilot Study Using an Improved Application System

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