New pharmacological strategies to restore hearing and treat tinnitus.
Recent advances in molecular pharmacology of the cochlea have lead to a much better understanding of the physiology, and especially the pathophysiology, of the sensorineural structures of the organ of Corti. Knowledge of the intimate molecular mechanisms of cellular dysfunction is of considerable use in the development of new therapeutic strategies. Herein, we summarize the mechanisms of sensory hair cell death after various injuries. Based on these molecular mechanisms, we propose novel therapeutic strategies to restore hearing. In addition to permanent hearing loss, exposure to noise or ototoxic drugs also induces tinnitus. We thus review recent findings obtained from a behavioral model of tinnitus in rats. In addition to providing evidence for the site and mechanism of generation of tinnitus induced by salicylate, these results support the idea that targeting cochlear N-methyl-D-aspartate receptors may represent a promising therapeutic strategy for treating tinnitus.
Guitton
Matthieu J
MJ
Physiopathologie et Thérapies des Déficits Sensoriels et Moteurs, Inserm U583 and Université de Montpellier 1, Montpellier, France.
Wang
Jing
J
Puel
Jean-Luc
JL
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D006198:Hair Cells, Auditory / Q000503:physiopathology; D034381:Hearing Loss / Q000188:drug therapy* / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D019782:Riluzole / Q000627:therapeutic use; D012459:Salicylates; D015398:Signal Transduction / Q000187:drug effects; D014012:Tinnitus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D018696:Neuroprotective Agents; D010455:Peptides; D012459:Salicylates; D019782:Riluzole; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C478085:D-JNKI-1