Local delivery of brain-derived neurotrophic factor on the perforated round window membrane in Guinea pigs: a possible clinical application.

HYPOTHESIS/BACKGROUND: Local delivery of neurotrophic factors on the intact round window membrane (RWM) of hair cell-deprived cochleas reduces degeneration of the cochlear nerve. In an animal model of profound hearing loss, we investigated whether this otoprotective effect could be enhanced by perforation of the RWM. Such method could be highly relevant for future clinical applications. METHODS: Guinea pigs were deafened by coadministration of kanamycin and furosemide. Two weeks after deafening, Gelfoam cubes infiltrated with brain-derived neurotrophic factor (BDNF) were deposited onto the RWM of the right cochlea. In the experimental condition, the RWM was perforated. Electrically evoked auditory brainstem responses (eABRs) were recorded weekly. Two or four weeks after Gelfoam placement, both left (untreated) and right (BDNF-treated) cochleas were processed for histology. RESULTS: In BDNF-treated cochleas, both with and without perforation, neural survival in the basal turn of the cochlea was significantly larger than in untreated cochleas. Amplitudes of electrically evoked auditory brainstem responses were larger in BDNF-treated cochleas with an RWM perforation than in those without a perforation and comparable to those of normal-hearing controls. Perforation did not lead to collateral cochlear damage. CONCLUSION: When considering clinical applications of neuroprotective agents such as BDNF, delivery on a perforated RWM seems to be a safe and effective option.

A guinea pig model of selective severe high-frequency hearing loss.

HYPOTHESIS: Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time. BACKGROUND: A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing. METHODS: Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks. RESULTS: After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable. CONCLUSION: An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.

Hearing preservation surgery: cochleostomy or round window approach? A systematic review.

OBJECTIVES/HYPOTHESIS: An increasing number of patients with low-frequency residual hearing are fitted with a cochlear implant. The challenge is to optimize cochlear implant device properties and develop atraumatic surgical techniques to preserve residual hearing. In view of the ongoing debate about the optimal procedure for opening the cochlea during cochlear implantation, we reviewed the evidence on the round window and the cochleostomy insertion techniques and compared their effects on postoperative residual hearing. DESIGN: Systematic review. METHODS: Electronic databases were systematically searched for relevant studies published up to January 2012. All studies reporting on residual hearing and hearing preservation surgery were included. RESULTS: Sixteen studies, with a total of 170 patients, were included. There were no studies directly comparing both surgical insertion techniques. The methodologic quality of the studies was poor and might be subjected to a high risk of bias. Because there were no studies directly comparing the 2 techniques and controlling for possible influencing factors, differences between studies might also be influenced by intersurgeon variance in many facets regarding cochlear implantation surgery. The available data show a postoperative low-frequency hearing loss ranging from 10 to 30 dB at 125, 250, and 500 Hz, regardless of surgical technique. The number of patients with a postoperative complete hearing preservation ranged from 0% to 40% for the cochleostomy group and from 13% to 59% in the round window group. CONCLUSION: The available data do not show that there is a benefit of one surgical approach over the other regarding the preservation of residual hearing. To provide solid evidence, a double-blind randomized trial is needed, which compares the clinical outcomes, notably the degree of hearing preservation, of both surgical approaches.

Spiral ganglion cell survival after round window membrane application of brain-derived neurotrophic factor using gelfoam as carrier.

Several studies have shown that treatment with various neurotrophins protects spiral ganglion cells (SGCs) from degeneration in hair-cell deprived cochleas. In most of these studies the neurotrophins are delivered by means of intracochlear delivery methods. Recently, other application methods that might be more suited in cochlear implant patients have been developed. We have examined if round window membrane application of gelfoam infiltrated with a neurotrophin resulted in SGC survival in deafened guinea pigs. Two weeks after deafening, gelfoam cubes infiltrated with 6 µg of brain-derived neurotrophic factor (BDNF) were deposited onto the round window membrane of the right cochleas. Electric pulses were delivered through an electrode positioned within the round window niche to electrically evoke auditory brainstem responses (eABRs). Two or four weeks after deposition of the gelfoam all cochleas were histologically examined. We found that local BDNF treatment enhances the survival of SGCs in the basal cochlear turn after two and four weeks. The treatment had no effect on SGC size or shape. In animals treated with BDNF, eABR amplitudes were smaller than in normal-hearing control animals and similar to those in deafened controls. We conclude that BDNF delivered by means of local gelfoam application provides a protective effect, which is limited compared to intracochlear delivery methods.