Effects of growth factors on the hair cells after ototoxic treatment of the neonatal mammalian cochlea in vitro.
The aim of this study was to test the possible regenerative potential of several molecules and growth factors such as retinoic acid (RA), insulin, epidermal growth factor (EGF) and transforming growth factors alpha (TGFalpha) and beta (TGFbeta) on the neonatal cochlea in vitro after neomycin intoxication. Our studies show that cochlear sensory epithelium behaves differently while maintained in various culture conditions, although we did not observe regeneration whatever the molecules or growth factors tested. The ototoxic action of neomycin in vitro produced a specific death of hair cells, except in the apical region. Organ of Corti of rats 3 days after birth always presented two regions that responded differently to the antibiotic: a widespread scar region extending from the basal cochlea up to the beginning of the apical turn, where most hair cells had disappeared, and a second region called the resistance region localized in the apex, and which was more or less developed depending on culture conditions. The length of the resistance region was modulated by molecules or growth factors added to the feeding solution suggesting that some of them could produce a protective action on hair cells against neomycin. Slight protection effects may be found with RA and insulin, however, the most definite protection results from the combination of insulin with TGFalpha as shown by the large increase in the length of the resistance region compared to organ of Corti treated with antibiotic alone. The tested molecules and growth factors did not promote cochlear hair cell regeneration in vitro after neomycin treatment, however some of them may offer a protective action against ototoxicity.
Romand
R
R
Laboratoire de Neurobiologie, Université Blaise Pascal-Clermont II, 63177 Aubière Cedex, France. romand@cicsun.univ-bpclermont.fr
Chardin
S
S
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000494:pharmacology; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006198:Hair Cells, Auditory / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008322:Mammals; D009355:Neomycin / Q000633:toxicity*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D006133:Growth Substances; D007004:Hypoglycemic Agents; D007328:Insulin; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D004815:Epidermal Growth Factor; D009355:Neomycin