Gordana Kel

Round window delivery of dexamethasone ameliorates local and remote hearing loss produced by cochlear implantation into the second turn of the guinea pig cochlea

Application of dexamethasone to the round window has been shown to ameliorate high frequency hearing loss resulting from the trauma of cochlear implantation in experimental animals, but elucidation of the factors influencing protection of the high frequencies has been confounded by the local trauma from electrode array insertion. In this experiment, a second turn cochleostomy and implantation was performed on guinea pigs, to examine protection in the basal turn without the confounding effect of local trauma, as well as to test the efficacy of hearing protection in the second cochlear turn. The implantation resulted in an increase in hearing thresholds across all frequencies examined (2-32 kHz). Local delivery of dexamethasone to the round window prior to implantation protected hearing across frequencies from 2 to 32 kHz. Auditory thresholds improved over the first week after surgery, and then remained stable for the month of the experiment. The protection of hearing in the basal turn increased with longer periods of drug application prior to implantation. The level of hearing protection in the second turn was similar irrespective of the time that the drug was applied, but was greater when a higher steroid concentration was used. It was concluded that steroids protect hearing in the basal turn of the cochlea even when there was no local trauma. The level of hearing protection in the second turn exceeded that expected from models of steroid diffusion through the cochlea, suggesting that inner ear surgery alters the distribution of dexamethasone within the cochlea.

Pre-Operative Intravenous Dexamethasone Prevents Auditory Threshold Shift in a Guinea Pig Model of Cochlear Implantation

Aim: To protect hearing during cochlear implantation with systemic administration of dexamethasone. Methods: Seventeen normal-hearing guinea pigs were randomly allocated to receive an intravenous injection of either normal saline (control), low- (0.2 mg/kg) or high- (2 mg/kg) dose dexamethasone 60 min prior to cochlear implantation. Auditory brainstem response (ABR) threshold shifts (2–32 kHz) were estimated between pre- and 4-week-postoperative levels. Results: ABR threshold shifts (8–32 kHz) observed in control and low-dose steroid groups were significantly reduced in the high-dose steroid group. Conclusions: A single, high-dose injection of intravenous dexamethasone protected hearing during cochlear implantation.

Targeted Therapy of the Inner Ear

Background: There is experimental evidence that targeted delivery of steroids to the inner ear can protect hearing during cochlear implant surgery. The best protection appears to be achieved through pre-treatment of the cochlea, but the time period required for treatment is long compared with the duration of surgery, and needs further optimization. The stability of hearing thresholds is determined over a 3-month period after hearing preservation cochlear implantation. Methods: Adult guinea pigs were implanted with a miniature cochlear implant electrode, and pure tone auditory brainstem response (ABR) thresholds were estimated in response to pure tones of 2–32 kHz immediately after surgery and at 1 week, 1 month and 3 months. Spiral ganglion cell (SGC) densities were estimated from mid-modular histological sections of the cochlea. Thirty minutes prior to implantation, a polymeric sponge (SeprapackTM, Genzyme) was loaded with either a 2% solution of dexamethasone phosphate or normal saline (control) and placed onto the round window. Results: Implantation was associated with an immediate elevation in thresholds across frequencies, with a full recovery below 2 kHz over the next week and a partial recovery of thresholds at higher frequencies. These thresholds remained unchanged for the next 3 months. There was an immediate and sustained reduction in the elevation of thresholds at 32 kHz in dexamethasone-treated animals. SGC densities were greater in steroid-treated animals than controls in the basal turn of the cochlea (at the region of implantation) 3 months after implantation. Conclusion: It is concluded that ABR thresholds remain stable for 3 months after cochlear implantation in the guinea pig, and that local application of steroids to the inner ear prior to implantation is an effective method of preserving SGC populations when there is residual hearing at the time of implantation.

Systemic immunity influences hearing preservation in cochlear implantation.

Hypothesis To determine whether a systemic immune response influences hearing thresholds and tissue response after cochlear implantation of hearing guinea pigs. Methods Guinea pigs were inoculated with sterile antigen (Keyhole limpet hemocyanin) 3 weeks before cochlear implantation. Pure-tone auditory brainstem response thresholds were performed before implantation and 1 and 4 weeks later. Dexamethasone phosphate 20% was adsorbed onto a hyaluronic acid carboxymethylcellulose sponge and was applied to the round window for 30 minutes before electrode insertion. Normal saline was used for controls. Cochlear histology was performed at 4 weeks after implantation to assess the tissue response to implantation. To control for the effect of keyhole limpet hemocyanin priming, a group of unprimed animals underwent cochlear implantation with a saline-soaked pledget applied to the round window. Results Keyhole limpet hemocyanin priming had no significant detrimental effect on thresholds without implantation. Thresholds were elevated after implantation across all frequencies tested (2–32 kHz) in primed animals but only at higher frequencies (4–32 kHz) in unprimed controls. In primed animals, dexamethasone treatment significantly reduced threshold shifts at 2 and 8 kHz. Keyhole limpet hemocyanin led to the more frequent observation of lymphocytes in the tissue response to the implant. Conclusion Systemic immune activation at the time of cochlear implantation broadened the range of frequencies experiencing elevated thresholds after implantation. Local dexamethasone provides partial protection against this hearing loss, but the degree and extent of protection are less compared to previous studies with unprimed animals.

Early cochlear response and ICAM-1 expression to cochlear implantation

Aim To examine the early cochlear response and intercellular cell adhesion molecule-1 (ICAM-1) expression to implantation of a cochlear electrode into the scala tympani. Background Understanding the early response of the cochlea to implantation may inform the duration which drug therapies should be delivered to protect hearing. Methods Guinea pigs were implanted with a cochlear electrode and survived 1, 2, or 7 days before they were euthanized, cochleae harvested, processed, and cryosectioned for light microscopy or ICAM-1 immunohistochemistry. Results On hematoxylin and eosin staining, scala tympani was characterized by the presence of fibrin and blood clot at 1 to 2 days after surgery, with a leukocytic infiltrate, primarily of neutrophils and macrophage-like cells. By 7 days after surgery, fibroblasts had infiltrated the clot, and the numbers of red blood cells (RBCs) and neutrophils had diminished. ICAM-1 expression was greatest in the lateral cochlear wall with highest expression found in the basal turn in the region of the electrode at 24 hours postimplantation. Conclusion The cochlear vasculature is maximally primed to recruit cells from the circulation, as evidenced by ICAM-1 expression levels, at 24 hours after cochlear implantation. This response is similar to that seen after other types of injury. Where cochlear implantation differs is the predominance of fibrin and clot early after electrode insertion before infiltration by fibroblasts by the end of the first postoperative week. These results suggest that anti-inflammatory drugs aimed at reducing the extravasation of immunecompetent cells into the cochlea must be effective over the first few days after surgery. Whether this can be achieved through preoperative treatment alone, or whether therapy will need to continue postoperatively, awaits further experimentation.

Contents Vol. 18, 2013

Maurizio Barbara, Rome Olivier Bertrand, Bron F. Owen Black, Portland Th omas Brandt, München Barbara Canlon, Stockholm John P. Carey, Baltimore Douglas A. Cotanche, Boston Cor W.R.J. Cremers, Nijmegen Norbert Dillier, Zürich Robert Dobie, Sacramento Manuel Don, Los Angeles Jill B. Firszt, St. Louis Andrew Forge, London Bernard Fraysse, Toulouse Rick Friedman, Los Angeles Bruce J. Gantz, Iowa City Pablo Gil-Loyzaga, Madrid Anthony W. Gummer, Tübingen James W. Hall III, Gainesville Joseph W. Hall III, Chapel Hill Michael Halmagyi, Camperdown Rudolf Häusler, Bern Vicente Honrubia, Los Angeles Gary D. Housley, Auckland Karl-Bernd Hüttenbrink, Köln Pawel J. Jastreboff , Atlanta Margaret A. Kenna, Boston Philippe P. Lefebvre, Liège Bernd Lütkenhöner, Münster Linda L. Luxon, London Geoff rey A. Manley, Oldenburg Alessandro Martini, Padova Jennifer R. Melcher, Boston Brian C.J. Moore, Cambridge David R. Moore, Nottingham Cynthia C. Morton, Boston Donata Oertel, Madison Kaoru Ogawa, Tokyo Stephen J. O’Leary, Parkville Alan R. Palmer, Nottingham Lorne S. Parnes, London, Ont. Jean-Luc Puel, Montpellier Ramesh Rajan, Monash Yehoash Raphael, Ann Arbor J. Th omas Roland, Jr., New York John J. Rosowski, Boston Rudolf Rübsamen, Leipzig Mario A. Ruggero, Evanston Leonard P. Rybak, Springfi eld Richard J. Salvi, Buff alo Robert V. Shannon, Los Angeles Guido F. Smoorenburg, Besse sur Issole Haim Sohmer, Jerusalem Olivier Sterkers, Clichy Istvan Sziklai, Debrecen Peter R. Th orne, Auckland Shin-ichi Usami, Matsumoto P. Ashley Wackym, Portland Tatsuya Yamasoba, Tokyo Fan-Gang Zeng, Irvine The Science of Hearing and Balance

Contents Vol. 14, 2009

Maurizio Barbara, Rome Olivier Bertrand, Bron F. Owen Black, Portland Th omas Brandt, München Barbara Canlon, Stockholm John P. Carey, Baltimore Douglas A. Cotanche, Boston Cor W.R.J. Cremers, Nijmegen Norbert Dillier, Zürich Robert Dobie, Sacramento Manuel Don, Los Angeles Jill B. Firszt, St. Louis Andrew Forge, London Bernard Fraysse, Toulouse Rick Friedman, Los Angeles Bruce J. Gantz, Iowa City Pablo Gil-Loyzaga, Madrid Anthony W. Gummer, Tübingen James W. Hall III, Gainesville Joseph W. Hall III, Chapel Hill Michael Halmagyi, Camperdown Rudolf Häusler, Bern Vicente Honrubia, Los Angeles Gary D. Housley, Auckland Karl-Bernd Hüttenbrink, Köln Pawel J. Jastreboff , Atlanta Margaret A. Kenna, Boston Philippe P. Lefebvre, Liège Bernd Lütkenhöner, Münster Linda L. Luxon, London Geoff rey A. Manley, Freising Alessandro Martini, Ferrara Jennifer R. Melcher, Boston Saumil N. Merchant, Boston Brian C.J. Moore, Cambridge David R. Moore, Nottingham Cynthia C. Morton, Boston Donata Oertel, Madison Kaoru Ogawa, Tokyo Stephen J. O’Leary, Parkville Alan R. Palmer, Nottingham Lorne S. Parnes, London, Ont. Jean-Luc Puel, Montpellier Ramesh Rajan, Monash Yehoash Raphael, Ann Arbor J. Th omas Roland, New York John J. Rosowski, Boston Rudolf Rübsamen, Leipzig Mario A. Ruggero, Evanston Leonard P. Rybak, Springfi eld Richard J. Salvi, Buff alo Robert V. Shannon, Los Angeles Guido F. Smoorenburg, Besse sur Issole Haim Sohmer, Jerusalem Olivier Sterkers, Clichy Istvan Sziklai, Debrecen Peter R. Th orne, Auckland Shin-ichi Usami, Matsumoto P. Ashley Wackym, Milwaukee Tatsuya Yamasoba, Tokyo Fan-Gang Zeng, Irvine Basic Science and Clinical Research in the Auditory and Vestibular Systems and Diseases of the Ear