Synergetic protective effects of glial cell line-derived neurotrophic factor combined with neurotrophin-3 in F-actin on hair cell after noise trauma

OBJECTIVE: To investigate if glial cell line-derived neurotrophic factor (GDNF) combined with neurotrophin-3 (NT-3) provides synergetic protection in filamentous actin (F-actin) on hair cell (HC) from acoustic trauma. METHODS: Guinea pigs were exposed to 4 kHz narrow band noise at 115 dB SPL for 4 h. Test group (n = 12) with a mixture of GDNF (100 ng/ml) and NT-3(2.5 micrograms/ml) or control group (n = 9) with artificial perilymph (AP) was delivered to the scala tympani via a mini-osmotic pump (0.5 microliter/h) for a total of 14 days. Auditory function was assessed by measuring thresholds of auditory brainstem responses (ABRs) elicited by clicks prior to surgery, 3 days after surgery (1 day before noise exposure) and 10 days following noise exposure (before animals were sacrificed), respectively. F-actin, labeled by rhodamine-phalloidin, was examined in the guinea pig cochlea using fluorescence microscopy for quantitative assessment of hair cell damage. RESULTS: There was a statistically significant increase the survival of out hair cell(P < 0.001, P < 0.01) and inner hair cell(P < 0.01, P < 0.01) and decrease in ABR threshold (P < 0.05, P < 0.01) in both the GDNF and NT-3 treated and untreated ear of animals. CONCLUSION: Our findings indicate that GDNF combined with NT-3 may effectively protect the inner ear from noise--induced hearing loss.