GUINEA-PIG AUDITORY NEURONS ARE PROTECTED BY GLIAL-CELL LINE-DERIVED GROWTH-FACTOR FROM DEGENERATION AFTER NOISE TRAUMA

For patients with profound hearing loss, cochlear implants have become the treatment of choice. These devices provide auditory information t hrough direct electrical stimulation of the auditory nerve. Prosthesis function depends on survival and electrical excitability of the cochl ear neurons. Degeneration of the auditory nerve occurs after lesions o f its peripheral target field (organ of Corti), specifically, includin g loss of inner hair cells (IHCs). There is now evidence that local tr eatment of the cochlea with neurotrophins may enhance survival of audi tory neurons after aminoglycoside-induced deafness. Glial cell line-de rived neurotrophic factor (GDNF) has recently been shown to be an impo rtant survival factor in other regions of the nervous system. By in si tu hybridization, we now show that IHCs of the neonatal and mature rat cochlea synthesize GDNF and that GDNF-receptor alpha, but not c-Ret, is expressed in the rat spiral ganglion. We also show that GDNF is a p otent survival-promoting factor for rat cochlear neurons in vitro. Fin ally, we examined GDNF efficacy to enhance cochlear-nerve survival aft er IHC lesions in vivo. We found that chronic intracochlear infusion o f GDNF greatly enhances survival of guinea pig cochlear neurons after noise-induced IHC lesions. Our results demonstrate that GDNF is likely to be an endogenous survival factor in the normal mammalian cochlea a nd it could have application as a pharmacological treatment to prevent secondary auditory nerve degeneration following organ of Corti damage . (C) 1998 Elsevier Science B.V. All rights reserved.