The protective effect of brain-derived neurotrophic factor after gentamicin ototoxicity

Hypothesis: Brain-derived neurotrophic factor (BDNF) influences the process of hair cell recovery in the vestibular sensory epithelium of the chinchilla after local application of gentamicin (GM). Background: Hair cell regeneration in the inner ear after GM ototoxicity has been demonstrated. However, the mechanisms responsible for this recovery have yet to be completely elucidated. This report examines the protective and proliferative effects that BDNF exerts on vestibular hair cells in experiments designed to further elucidate the mechanisms of hair cell regeneration. Methods: The inner ears of three separate groups of chinchillas were treated with GM only, GM and BDNF simultaneously, and GM followed by BDNF 1 week later. The numbers of hair and supporting cells in the horizontal cristae of each group were then estimated at 1, 2, 4, and 8 weeks, and the data were compared. Results: Type I hair cells after GM treatment completely disappeared. After simultaneous BDNF and GM treatment, their numbers decreased to 23% at 1 week and progressively disappeared by week 8. When BDNF was applied 1 week after GM administration, type I hair cells recovered to 12% at week 4 and 28% at week 8. Type II hair cells after GM treatment decreased to 15%, but recovered to 83% 4 weeks later. Simultaneous administration of BDNF and GM prevented the ototoxic effects of GM alone. When BDNF was administered 1 week after GM, type II hair cell recovery was accelerated and was greater than after GM alone (81% versus 18%). Supporting cells after GM treatment decreased to 74% at 1 week after treatment, recovered to 91% at 2 weeks, and remained at 86% at 4 weeks and 85% at 8 weeks. With the simultaneous administration of BDNF and GM, supporting cells significantly decreased at 2 weeks after treatment (63%), but recovered to normal by week 8. Conclusions: These results suggest that BDNF provided simultaneously with GM minimizes the ototoxic effect of GM on type II hair cells. The increase in the number of new hair cells when BDNF is provided after ototoxic damage is evidence of the proliferative capacity of this neurotrophic factor.