Early hearing protection by brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) protects the inner ear from PaExoA (exotoxin A from Pseudomonas aeruginosa)-induced sensory neural hearing loss when administered 12 h after exotoxin, but not after 72 h.BDNF is a peptide in the neurotrophin family with protective effects against noise-induced hair cell loss and toxic inner ear damage following exposure to cisplatin. The exotoxin A (PaExoA) from P. aeruginosa, the most common microorganism in chronic suppurative otitis media, induces sensorineural hearing loss in rats. Previous study showed that, when given simultaneously with the exotoxin, BDNF protected the inner ear from damage. The aim of this study was to determine if BDNF has a protective effect when given 12-72 h after PaExoA.Five groups of Sprague-Dawley rats were used. The three control groups (n = 16) were as follows. Group 1 (n = 8) received 15 µg/20 µl PaExoA; group 2 (n = 5) received 20 µg/20 µl PaExoA; and group 3 (n = 3) received 25 µg/20 µl PaExoA injected into the round window niche. There were two treatment groups (n = 12): group A (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 12 h later; group B (n = 6) received 15 µg/20 µl PaExoA and 4 µg/20 µl BDNF 72 h later. Brainstem response audiometry (ABR) was performed on day 0 (control), and repeated on days 7, 14, 21, 28, and 35 to analyze the thresholds shifts.Exposure to 15 µg/20 µl PaExoA caused persistent and significant ABR impairment in controls when measured after 35 days. A single dose of BDNF given 12 h after PaExoA reduced hearing loss significantly, but when BDNF was given 72 h after PaExoA no protective effect was evident.