Riluzole rescues cochlear sensory cells from acoustic trauma in the guinea-pig

Acoustic trauma is the major cause of hearing loss in industrialised nations. We show in guinea-pigs that sound exposure (6 kHz, 120 dB sound pressure level for 30 min) leads to sensors cell death and subsequent permanent hearing loss. Ultrastructural analysis reveals that degeneration of the noise-damaged hair cells involved different mechanisms. including typical apoptosis, autolysis and, to a lesser extent, necrosis. Whatever the mechanisms, a common feature of noise damage to hair cells was mitochondrial alteration. Riluzole (2-amino-6-trifluoromethox benzothiazole) is a neuroprotective agent that prevents apoptosis- and necrosis-induced cell death. Perfusion of riluzole into the cochlea id an osmotic minipump prevents mitochondrial damage and subsequent translocation of cytochrome c, DNA fragmentation. and hair cell degeneration. This as confirmed by functional tests showing a clear dose-dependent reduction (ED50 = 16.8 muM) of permanent hearing loss and complete protection at 100 muM. Although less efficient than intracochlear perfusion, intraperitoneal injection of riluzole rescues the cochlea within a therapeutic window of 24 h after acoustic trauma. These results show that riluzole is able to prevent and rescue the cochlea from acoustic trauma. It may thus be an interesting molecule for the treatment of inner ear injuries. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.