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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
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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-
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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
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