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Document downloaded from http://www.elsevier.es, day 09/05/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. International Symposium on Inner Ear Research Madrid (Spain), November 10, 2007 (linked to the 58th National Meeting of the Spanish Society of E.N.T.) New Frontiers on Inner Ear Regeneration, Protection and Neuroplasticity OBJECTIVES: To show the main advances on inner regeneration and neuroplasticity (receptor or auditory pathway) that have been obtained during the recent years and that could be useful or applied in clinics. The meeting will be addressed to people involved in inner ear research but, in particular, to ENT doctors working on cochlear/nuclear implants, micropumps, etc. The attendance of young people (MD or PhD students or young) will be encouraged (no inscription costs, also lunches will be free for them, low cost lodging were offered!). SCIENTIFIC PROGRAM: Chairmen of the Meeting : Prof. Pablo Gil-Loyzaga Professor of Neurobiology of Hearing. Dpt. Ophtalmology and Oto-Rhino-Laryngology. University Complutense of Madrid (Spain) President of Research Commision of the Spanish Society of E.N.T. Conference Title: Cellular and Molecular Bases of Neuroplasticity Prof. Matti Anniko Professor of Otorhinolaryngology. University of Uppsala (Sweden) Editor-in-Chief Acta Oto-Laryngologica (Stockholm) Honorary Member of the Spanish Society of E.N.T. Invited Speakers: Prof. Remy Pujol Professor Emeritus. Faculty of Medicine. University of Montpellier (Francia) Conference Title: “New challenges on inner ear research for the XXI century” Prof. Edwin W. Rubel Professor of Hearing Science. Viirginia Merrill Bloedel Hearing Reserch Center. Professor of OtolaryngologyHead and Neck Surgery, Physiology and Biophysics, and Psychology, University of Washington, Seattle, Washington, USA Conference Title: “Hair cell regeneration in the inner ear - History and current perspectives” Prof. Allen Ryan Professor- Director of Research. Dept. of Otorhinolaryngology/Head and Neck Surgery. University of California – San Diego (U.S.A.) Conference Title: “Transplantation of cells into the inner ear” Prof. Philippe Lefevbre and Dr. Brigitte Malgrange Professor of Otorhinolaryngology. Dept. of Otorhinolaryngology. University of Liege (Bélgica) Prof. Jochen Schacht Professor and Director Kresge Hearing Research Institute. University of Michigan (U.S.A.) Conference Title: “Drug- induced hearing loss and its prevention” Prof. Jean Luc Puel Professor University of Montpellier (Francia). Director Unity of “Inner Ear” Inserm 583. Director of the Audioprothesis School of Montpellier University. Conference Title: “Local therapy for protection of the inner ear: trans-tympanic and cochlear implant approaches” Prof. Thomas Van de Water Professor. Department of Otorhinolaryngology. University of Miami Ear Institute (U.SA) Director Cochlear Implant Research Program Conference Title: “Mechanisms of Hearing Loss from Trauma and Ototoxins: Otoprotective Therapies from the Laboratory to the Clinic “ Prof. Pablo Gil-Loyzaga Professor of Neurobiology of Hearing. Dpt. Ophtalmology and Oto-Rhino-Laryngology. University Complutense of Madrid (Spain) President of Research Commision of the Spanish Society of E.N.T. Conference Title: “Bases of neuroplasticity: brainstem effects of cochlear dammage” Prof. Lionel Collet Professeur et Chef Service ORL. Hopital Edouard Herriot de Lyon (Francia). Directeur Unité CNRS “ Neuro-Sciences et Système Sensoriel “ Rector Universidad de Lyon (Francia) Conference Title: “Plasticity of tonotopic maps in humans: Influence of hearing-loss, hearing-aids and cochlear implants” Acta Otorrinolaringol Esp. 2007;58(Espec Congr):159-61 159 Document downloaded from http://www.elsevier.es, day 09/05/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. 58 Congreso Nacional de la Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial Prof. Miguel Merchan Professor University of Salamanca (España). Director of the Neuroscience Institute of Castilla-León. Conference Title: “Changes in the inferior colliculus after unilateral ablation of the auditory cortex. An stereological, RT-PCR and prepulse inhibition study”. SYMPOSIUM PUBLICATION: Prof. Matti Anniko has kindly offered the publication of a summary of the conferences of the Symposium in Acta Otolaryngologica (Stockholm). Guidelines for authors will follow in the next future. RESUMENES DRUG- INDUCED HEARING LOSS AND ITS PREVENTION Prof. Jochen Schacht Treatment with aminoglycoside antibiotics may cause auditory or vestibular side effects through destruction of hair cells. Compelling evidence from animal models suggests that reactive oxygen species are part of the initial mechanisms that trigger apoptotic and necrotic cell death in the inner ear. Consequently, antioxidants protect against aminoglycoside- induced hearing loss in animals. While clinical trials have long confirmed the ototoxicity of aminoglycosides in human, a trial on protection was only recently concluded. Based on the finding that salicylate acted as a protectant in animals, the efficacy of aspirin (acetyl salicylate) was tested in a randomized doubleblind placebo-controlled study in patients receiving gentamicin for acute infections. A total of 195 patients completed the study. Fourteen of 106 patients (13%) met the criterion of hearing loss in the placebo group while only 3/89 (3%) were affected in the aspirin group (p = 0.013). Aspirin did not influence gentamicin serum levels or the course of therapy. MECHANISMS OF HEARING LOSS FROM TRAUMA AND OTOTOXINS: OTOPROTECTIVE THERAPIES FROM THE LABORATORY TO THE CLINIC Prof. Thomas Van de Water Oxidative stress is generated within the auditory hair cells of the cochlea in response to either a physical trauma or following exposure to a toxic level of an ototoxin. Oxidative stress causes internal damage within the exposed hair cell and eventually can trigger programmed cell death which results in a permanent loss of hearing. Otoprotective therapies focus on the prevention of the loss of hair cells and their eventual self-repair and restoration to function. Two treatment strategies and their clinical applications will be discussed: 1) blocking of programmed cell death signal cascades; and 2) anti-inflammatory therapies. 160 Acta Otorrinolaringol Esp. 2007;58(Espec Congr):159-61 TRANSPLANTATION OF CELLS INTO THE INNER EAR Prof. Allen Ryan Stem cells provide a potential means for the replacement of damaged cells in many organ systems, including the inner ear. The flexibility of stem cells can be manipulated to produce many types of cells that are important for inner ear function. Placing these cells into the damaged inner ear is also quite feasible. However, achieving integration into the appropriate cellular sites is more challenging. Current progress in conversion of cells to inner ear phenotypes and in transplantation of cells into labyrinthine tissues will be discussed. HAIR CELL REGENERATION IN THE INNER EAR: HISTORY AND CURRENT PERSPECTIVES Prof. Edwin W Rubel In 1987-88 a paradigm shift occurred in our views of future therapies for hearing loss. Before this time, it was thought that hearing loss and balance dysfunction due to loss if inner ear hair cellsis permanent. While these problems could be treated by a variety of corrective measures such as amplification or bypassing the missing hair cells and directly stimulating the nerve, normal biological function could not be restored because of the inability to replace missing hair cells. In 1987-88 two laboratories simultaneously discovered that birds spontaneously regenerate new hair cells when the native hair cells are killed by aminoglycoside or intense noise exposure. This discovery issued in a new era in which laboratories throughout the world sought to discover the functional and molecular properties of hair cell regeneration in birds and other non-mammalian vertebrates and to find ways to coax the mammalian inner ear into this capability. I will provide an update on this work from our laboratories at the Virginia Merrill Bloedel Center and other laboratories. Studies of birds and other nonmammalian vertebrates are providing data on the molecular and cellular pathways underlying hair cell regeneration in these species. In particular, studies have revealed that the pathways underlying the decision of newly produced cells or dedifferentiated cells to populate the sensory epithelium with new hair cells rather than supporting has use the same signaling pathways as the embryonic inner ear. This information is being used in the mammalian ear to guide genetic manipulations that are providing promising new insights on ways that it might be possible to restore hearing and balance. Supported by the National Institute for Deafness and other Communication Diseases (NIDCD), the Oberkotter Foundation and the Virginia Merrill Bloedel Hearing Research Center. CELLULAR AND MOLECULAR BASES OF NEUROPLASTICITY: BRAINSTEM EFFECTS AFTER COCHLEAR DAMMAGE Prof. Pablo Gil-Loyzaga It is now increasing the interest on neuroplasticity and nerve regeneration within the auditory receptor and pathway. The receptor and the auditory pathway are organized by highly complex circuits that appear during embryo deve- Document downloaded from http://www.elsevier.es, day 09/05/2017. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. 58 Congreso Nacional de la Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial lopment. During cochlear development a relevant nerve fiber sprouting reach the sensory receptor. Somo of that fibers will remain along the adult life, while other transitory fibers dissapear. However, both stable and transitory fibers, as well as developing sensory cells, express, and probably release, their corresponding neurotransmitters that could be involved in neuroplasticity. Cell culture experiments added relevant information, therefore the in vitro administration of glutamate or GABA to isolated spiral ganglion neurons clearly modified neurite sprouting. Section of the auditory nerve immediately resulted in the cochlear brainstem nuclei damage, however and increase of functional activity was observed at the controlateral nuclei. After two weeks of neuronal degeneration and nerve fiber reorganization a significant nerve phylopodia sprouting was detected by the presence of small new fiber terminals that showed a remarkable GAP-43 expression. Cochlear braistem neuroplasticity in the adulthood and its relevance for cochlear implant are discussed. CHANGES IN THE INFERIOR COLLICULUS AFTER UNILATERAL ABLATION OF THE AUDITORY CORTEX. AN STEREOLOGICAL, RT-PCR AND PREPULSE INHIBITION STUDY Prof. Miguel Merchán The descending projection from the auditory cortex (AC) to the inferior colliculus (IC) is glutamatergic (Po- tashner, 1995). This projection is dense, symmetrical, bilateral, and topographically organized. It terminates in all three main divisions of the IC. The AC was ablated unilaterally in 27 wistar rats ( b.w., 260 g) under stereotaxic control. In all 27 cases, the startle reflex was assessed prior surgery (Lee et al., 1996) and subsequent perfusion. Animals were sacrificed after 15, 95 and 180 days post-ablation (n=4 in each experimental group). The IC in each group (including, a control group) was inmunostained for CR and each group was analyzed with stereology The stereological data showed a significative increase in the number of stained neurons up to 6 moths postlesion in all IC subdivisions bilaterally. The major increase was seen in the dorsal cortex, and then in the external cortex and the least in the central nucleus of the IC. Three control cases and 2 groups of 3 lesioned animals were used to study RT-PCR at 95 and 185 days postlesion. The analysis showed changes in the postsynaptic receptor subunits for the ionotrophic glutamatergic receptors (AMPA; NMDA and Kainate) three months postlesion. The data shows a lost of expression for different subunits that recovers at 6 months postlesion. The PPI data demonstrated a lack of response for the tested frequencies and a total recovery after 180 days postlesion. Acta Otorrinolaringol Esp. 2007;58(Espec Congr):159-61 161