
      <div class="modal-header">
        <button type="button" class="close" data-dismiss="modal"><span aria-hidden="true">&times;</span><span class="sr-only">Close</span></button>
        <h4 class="modal-title" id="myModalLabel">CONFERENCE ABSTRACT (POSTER PRESENTER)</h4>
        <h5>Drug Discovery in Preclinical Research</h5>
      </div>
      <div class="modal-body">
        <img src="images/speakers/avatar.gif">
        <h4>AMPLITUDE OF THE RESPONSE OF THE EVOKED POTENTIAL OF THE INFERIOR COLLICULUS AS A MARKER
</h4>
        
        <p><strong>Sylvie Cosnier-Pucheu</strong>, Philippe Larroze-Chicot, Aurore Marie, Yves Cazals, Arnaud Norena and John Alam</p>
<p>Department of Research, Cilcare, Montpellier, France</p>
<h4>Abstract</h4>


<p>Tinnitus is highly complex, and difficult to treat, in part due to the fact that the underlying causes and mechanisms remain elusive. Noise exposure leads to an immediate hearing loss and is followed by changes of cellular properties within the central auditory pathway described as a factor of the onset of tinnitus. Tinnitus is not directly observable in animals, and is usually assessed through changes in behavioural models. In the described study, we focused on measuring electrophysiological parameters and especially the amplitude of the response of the evoked potential of the inferior colliculus (IC), a midbrain structure, which may reflect a reorganization of neural activity observed in presence of tinnitus. A hundred Long Evans rats, anesthetized with isoflurane, were exposed to a bilateral acoustic trauma of 1 hour, 120dB sound pressure level (SPL), two octave band noise (4-16kHz) centered at 8 kHz. Electrodes were implanted on the scalp of the animals to measure the CAP of the auditory nerve (VCN) and the evoked potential from the IC at ten frequencies: 2, 4, 6, 8, 10, 12, 16, 20, 26, and 32 kHz with burst levels from 90 to 10 dB at days 3, 7, 10, 14 and 16 after acoustic trauma. The exposure produced approximately 20 to 30 dB of transient CAP threshold shift measured 24 hours after the noise exposure. After 3 days, the threshold values returned, to their baselines. This observed transitory threshold shift (TTS) represent the targeted conditions to induce tinnitus. An increase of the amplitude of the response of the evoked potential of the IC is observed at 6kHz and is significant at day 3 and day 14 compared to the values observed in Sham rats. These results could indicate the presence of tinnitus as described by some authors in the literature. Several publications suggest that acoustic trauma could result in damages to auditory system due to the activation of MAPK and BNDF in the IC. In this study we tested a p38 MAPK alpha inhibitor and use the measure of the amplitude of the response of the evoked potential of the IC as a marker for a first proof of concept of a drug candidate in the treatment of tinnitus. Two doses of the investigated compound administered twice daily from day 8 post-trauma and during 7 days induced some non-significant effects in the inferior colliculus (IC) parameter at 6kHz, which could indicate an effect on tinnitus. This study demonstrates that electrophysiological parameters and especially the amplitude of the response of the evoked potential of the IC could become an objective read out to assess the effect of new therapeutic compounds on tinnitus in preclinical studies. This assumption will be further confirmed in another study looking at the correlation of this electrophysiological parameter with referenced behavioral models.</p>

<p><strong>Keywords:</strong> Tinnitus, MAPK, inferior colliculus, electrophysiological parameter.</p>

        </div>