Riluzole rescues cochlear sensory cells from acoustic trauma in the guinea-pig
Section snippets
Experimental procedures
These experiments were designed to test whether riluzole can rescue the cochlea from acoustic trauma in guinea-pigs. The care and use of animals followed the animal welfare guidelines of the ‘Institut National de la Santé et de la Recherche Medicale’ (INSERM), and under the approval of the French ‘Ministère de l’Agriculture et de la Forêt’. All efforts were made to minimise the number of animals used and their suffering.
Electrophysiological studies
In the non-perfused contralateral control ear, the average hearing thresholds measured 20 min after acoustic trauma were elevated to between 60 and 70 dB in the higher frequencies of the CAP audiogram, with a maximum threshold elevation between 10 and 16 kHz (Fig. 2A). During the first 24 h following the acoustic trauma, there was a partial recovery of CAP thresholds of around 30 dB. Over the next 24 h, CAP thresholds continued to recover slowly, by around 10 dB, to reach a final threshold
Discussion
In our model of acoustic trauma in the guinea-pig, 30 min of a 6 kHz tone at 120 dB SPL induced a PTS that affected a wide range of frequencies, between 6 and 16 kHz. However, maximal hair cell loss was restricted to a precise region, 14–16 mm from the apex, which was the site maximally stimulated by our noise paradigm. Fragmented hair cell nuclei were observed in the same region using morphological analyses and specific DNA labelling. Ultrastructural examination revealed mitochondrial damage
Acknowledgements
The authors want to thank the anonymous reviewers for their comments and constructive criticisms. Help from Dr Adam Doble in interpreting the data was highly appreciated. The authors are also indebted to Jérôme Ruel, Régis Nouvian and Matthieu Guitton for their helpful discussions concerning the experiments, Ruth Lloyd Faulconbridge and Jean Louis Pasquier for editing work and Sabine Ladrech, Ghyslaine Humbert and Nicole Renard for their technical assistance.
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2013, NeuroscienceCitation Excerpt :Despite years of investigation, the mechanisms underlying PTS are not fully understood. After acoustic trauma, direct mechanical damage and indirect metabolic alterations occur in cochlear hair cells (Schuknecht, 1993; Borg et al., 1995; Duan et al., 2002; Wang et al., 2002). Oxidative stress and anti-oxidative protective mechanisms might play key roles in noise-induced biochemical responses in cochlear cells (Yamane et al., 1995; Shi and Nuttall, 2003; Henderson et al., 2006).