Cochlear Implantation in the Guinea Pig

Cochlear implants are highly efficient devices that can restore hearing in subjects with profound hearing loss. Due to improved speech perception ...

Medical University of Vienna

In the present study the glycosylation pattern of the middle ear mucosa (MEM) of guinea pigs, an approved model for middle ear research, was characterized with the purpose to identify bioadhesive ligands which might prolong the contact time of drug delivery systems with the middle ear mucosa (MEM). To assess the utility of five fluorescein labeled plant lectins with different carbohydrate specificities as bioadhesive ligands, viable MEM specimens were incubated at 4°C and the lectin binding capacities were calculated from the MEM-associated relative fluorescence intensities. Among all lectins under investigation, fluorescein-labeled wheat germ agglutinin (F-WGA) emerged as the highest bioadhesive lectin. In general, the accessibility of carbohydrate moieties of the MEM followed the order: sialic acid and N-acetyl-d-glucosamine (WGA)>mannose and galactosamine (Lensculinaris agglutinin)>N-acetyl-d-glucosamine (Solanumtuberosum agglutinin)>fucose (Ulexeuropaeus isoagglutinin I)>terminal mannose α-(1,3)-mannose (Galanthusnivalis agglutinin). Competitive inhibition studies with the corresponding carbohydrate revealed that F-WGA-binding was inhibited up to 90% confirming specificity of the F-WGA-MEM interaction. The cilia of the MEM were identified as F-WGA binding sites by fluorescence imaging as well as a z-stack of overlays of transmission, F-WGA- and nuclei-stained images of the MEM. Additionally, co-localisation experiments revealed that F-WGA bound to acidic mucopolysaccharides of the MEM. All in all, lectin-mediated bioadhesion to the MEM is proposed as a new concept for drug delivery to prolong the residence time of the drug in the tympanic cavity especially for successful therapy for difficult-to-treat diseases such as otitis media.

Determination of the glycosylation-pattern of the middle ear mucosa in guinea pigs.

Selective glucocorticoid receptor modulators (SEGRMs) comprise a novel class of drugs promising both reduced side effects and similar pharmacological potency relative to glucocorticoids, which presently serve as the only clinical treatment for many otologic disorders. In the first otologic SEGRM experiment in an animal model of noise trauma, we compare the effects of Compound A (a SEGRM) and dexamethasone (potent glucocorticoid).

Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A.

It has been shown that glucocorticoids reduce the hearing threshold shifts associated with cochlear implantation. Previous studies evaluated the administration of glucocorticoids immediately before surgery or the repeated pre- or perioperative systemic application of glucocorticoids. The aim of this study was to evaluate the effects of a sustained release dexamethasone hydrogel in hearing preservation cochlear implantation. To address this issue, a guinea pig model of cochlear implantation was used. 30 normal hearing pigmented guinea pigs were randomized into a group receiving a single dose of a dexamethasone/poloxamer407 hydrogel one day prior to surgery, a second group receiving the hydrogel seven days prior to surgery and a control group. A silicone cochlear implant electrode designed for the use in guinea pigs was inserted to a depth of 5 mm through a cochleostomy. Compound action potentials of the auditory nerve (frequency range 0.5-32 kHz) were measured preoperatively, directly postoperatively and on postoperative days 3, 7, 14, 21 and 28. Following the last audiometry, temporal bones were harvested and histologically evaluated. Dexamethasone hydrogel application one day prior to surgery resulted in significantly reduced hearing threshold shifts at low, middle and high frequencies measured at postoperative day 28 (p < 0.05). Application of the hydrogel seven days prior to surgery did not show such an effect. Dexamethasone application one day prior to surgery resulted in increased outer hair cell counts in the cochlear apex and in reduced spiral ganglion cell counts in the basal and middle turn of the cochlea, a finding that was associated with a higher rate of electrode translocation in this group. In this study, we were able to demonstrate functional benefits of a single preoperative intratympanic application of a sustained release dexamethasone hydrogel in a guinea pig model of cochlear implantation.

Article	Year
Determination of the glycosylation-pattern of the middle ear mucosa in guinea pigs. International journal of pharmaceutics\| PubMed ID: 25724132	2015
Noise trauma and systemic application of the selective glucocorticoid receptor modulator compound A. Journal of negative results in biomedicine\| PubMed ID: 27164957	2016
Effects of sustained release dexamethasone hydrogels in hearing preservation cochlear implantation. Hearing research\| PubMed ID: 27519654	2016

Chengjing Zhu

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