Protective effect of brain-derived neurotrophic factor against the ototoxicity of Pseudomonas aeruginosa exotoxin A.
OBJECTIVE
The protective effect of brain-derived neurotrophic factor (BDNF) against the ototoxicity resulting from exposure of Pseudomonas aeruginosa exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF and N(G)-nitro-L-arginine methyl ester (L-NAME) was also investigated.


METHODS
Six groups of albino rats were instilled through the tympanic membrane into the round window niche with the following solutions: saline; PaExoA; BDNF; L-NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME. Frequency-specific (2-31.5 kHz) auditory brainstem responses were used to obtain the hearing thresholds before and 2, 5 and 15 days after instillation.


RESULTS
PaExoA penetrated from the middle ear into the cochlea, causing initially mixed hearing loss, followed by persistent sensorineural hearing loss. This impairment was blocked by BDNF at 6, 8 and 10 kHz on Day 2 and at 8 kHz on Day 5. L-NAME given in combination with BDNF did not show any additional protective effect. There were no significant differences in the thickness of the round window membrane between control ears and those in each instillation group.


CONCLUSIONS
Our results suggest that BDNF may protect against cochlear damage caused by PaExoA in the middle turns of the ear.
Maeta
Manabu
M
Department of Otorhinolaryngology and Head & Neck Surgery, Uppsala University Hospital, Uppsala, Sweden. m-maeta@cc.okayama-u.ac.jp
Anniko
Matti
M
D036002:ADP Ribose Transferases / Q000633:toxicity*; D000818:Animals; D001301:Audiometry, Pure-Tone; D001305:Auditory Fatigue / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003056:Cochlear Nerve / Q000187:drug effects; D004432:Ear, Middle / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005098:Exotoxins / Q000633:toxicity*; D006319:Hearing Loss, Sensorineural / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010898:Pitch Perception / Q000187:drug effects*; D012405:Round Window, Ear / Q000187:drug effects; D037521:Virulence Factors / Q000633:toxicity*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D019208:Brain-Derived Neurotrophic Factor; D005098:Exotoxins; D019331:NG-Nitroarginine Methyl Ester; D018696:Neuroprotective Agents; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A