Mechanical overstimulation causes acute injury and synapse loss followed by fast recovery in lateral-line neuromasts of larval zebrafish.

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hr displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.

Restoration of middle-ear input in fluid-filled middle ears by controlled introduction of air or a novel air-filled implant.

The effect of small amounts of air on sound-induced umbo velocity in an otherwise saline-filled middle ear (ME) was investigated to examine the efficacy of a novel balloon-like air-filled ME implant suitable for patients with chronically non-aerated MEs. In this study, air bubbles or air-filled implants were introduced into saline-filled human cadaveric MEs. Umbo velocity, a convenient measure of ME response, served as an indicator of hearing sensitivity. Filling the ME with saline reduced umbo velocity by 25-30 dB at low frequencies and more at high frequencies, consistent with earlier work (Ravicz et al., Hear. Res. 195: 103-130 (2004)). Small amounts of air (∼30 µl) in the otherwise saline-filled ME increased umbo velocity substantially, to levels only 10-15 dB lower than in the dry ME, in a frequency- and location-dependent manner: air in contact with the tympanic membrane (TM) increased umbo velocity at all frequencies, while air located away from the TM increased umbo velocity only below about 500 Hz. The air-filled implant also affected umbo velocity in a manner similar to an air bubble of equivalent compliance. Inserting additional implants into the ME had the same effect as increasing air volume. These results suggest these middle-ear implants would significantly reduce conductive hearing loss in patients with chronically fluid-filled MEs.

Middle-ear mechanics of Type III tympanoplasty (stapes columella): I. Experimental studies.

OBJECTIVE: To investigate the mechanics of Type III tympanoplasty by developing a cadaveric temporal bone model. BACKGROUND: Type III stapes columella tympanoplasty involves the placement of a tympanic membrane graft, usually made of temporalis fascia, directly onto the stapes head. The procedure is usually done in conjunction with a canal wall down mastoidectomy. Postoperative hearing results vary widely, with air-bone gaps of 10 to 60 dB. The structural features responsible for the wide range in hearing results have not been systematically investigated. METHODS: Canal wall down Type III procedures were performed in eight cadaveric temporal bones. Acoustic stimuli were presented in the ear canal, and round window velocity VRW (used as an index of hearing) was measured, while systematically varying stapes mobility, mechanical properties of tympanic membrane graft, and tightness of connection between tympanic membrane graft and stapes. The effect of interposing a thin cartilage disc between the tympanic membrane graft and stapes head was also assessed. RESULTS: When the middle ear was aerated and the stapes was mobile, VRW was 15 to 30 dB lower than in an intact, normal ear. Stapes fixation led to a significant reduction in VRW; reduction was greatest at low frequencies. There was little effect of varying the tightness of connection between the tympanic membrane graft and stapes head. Sound energy was transmitted from the graft to the stapes as long as the graft was in physical contact with the stapes head. Different tympanic membrane graft materials with a range of mechanical properties (stiffness and mass) resulted in little variation in VRW. Interposing a thin cartilage disc between the tympanic membrane graft and stapes improved VRW in the lower frequencies by 5 to 10 dB. The authors hypothesize that the disc acted to increase the effective vibrating area of the graft. CONCLUSIONS: The feasibility of using a cadaveric temporal bone model to study the mechanics of Type III tympanoplasty was demonstrated. A mobile stapes and aerated middle ear were essential for a successful Type III tympanoplasty. There was little effect of varying the mechanical properties of the tympanic membrane graft or changing the tightness of connection between the graft and stapes head. Improved results were achieved by interposing a thin cartilage disc between the graft and stapes head to increase the effective vibrating area of the graft.

Middle ear mechanics of Type III tympanoplasty (stapes columella): II. Clinical studies.

OBJECTIVES: To determine the structural features that are responsible for the large variation in postoperative hearing results after Type III stapes columella tympanoplasty, to compare the clinical results after Type III tympanoplasty with predictions based on experimental investigations using a temporal bone model, and to investigate the effectiveness of a modification in surgical technique for Type III reconstruction. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. INCLUSION CRITERIA: The ear was healed with an intact tympanic membrane graft; the status of the stapes was known, whether mobile or fixed; and the postoperative status of aeration of the middle ear was known, whether aerated or not. MAIN OUTCOME MEASURE: Air-bone gap at frequencies 250, 500, 1,000, 2,000 and 4,000 Hz. RESULTS: In ears with temporalis fascia graft onto stapes head: mobile stapes and aerated middle ear (n = 34), mean air-bone gaps at audiometric frequencies were 15 to 30 dB, consistent with predictions of the experimental model; mobile stapes and nonaerated middle ear (n = 16), large air-bone gaps of 35 to 55 dB; fixed stapes and aerated middle ear (n = 4), large air-bone gaps of 30 to 50 dB; fixed stapes and nonaerated middle ear (n = 2), large air-bone gaps of 30 to 70 dB. In ears with a fascia-cartilage graft onto stapes head, where a thin disc of meatal cartilage, 0.3 to 0.5 mm thick and 4 to 6 mm in diameter was interposed between the fascia graft and the stapes head: mobile stapes and aerated middle ear (n = 9), mean air-bone gaps at audiometric frequencies were 10 to 25 dB, about 5 dB better at 250, 500, and 2,000 Hz than in ears with only a fascia graft ( <0.05), improvement consistent with that observed experimentally when a thin cartilage disc was used in the temporal bone model, hypothesis that the cartilage increased the effective vibrating area of the graft; mobile stapes and nonaerated middle ear (n = 2), air-bone gaps were 40 to 50 dB. CONCLUSIONS: Large air-bone gaps of 30 to 70 dB occurred as a result of stapes fixation, nonaeration of the middle ear, or both. When the stapes was mobile and the middle ear was aerated, a fascia graft resulted in air-bone gaps of 15 to 30 dB. Interposing a thin disc of cartilage between the fascia graft and stapes head to improve the effective vibrating graft area gave better hearing, with air-bone gaps of 10 to 25 dB. The clinical Type III results were consistent with predictions based on experimental investigations of mechanics of the Type III procedure in a temporal bone model.