Protective effect of brain-derived neurotrophic factor against the ototoxicity of Pseudomonas aeruginosa exotoxin A

Acta Otolaryngol. 2003 Jan;123(1):14-9.

Abstract

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.

Material and 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.

Conclusion: Our results suggest that BDNF may protect against cochlear damage caused by PaExoA in the middle turns of the ear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / toxicity*
  • Animals
  • Audiometry, Pure-Tone
  • Auditory Fatigue / drug effects
  • Auditory Threshold / drug effects
  • Bacterial Toxins / toxicity*
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cochlear Nerve / drug effects
  • Ear, Middle / drug effects*
  • Evoked Potentials, Auditory, Brain Stem / drug effects*
  • Exotoxins / toxicity*
  • Hearing Loss, Sensorineural / physiopathology*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Neuroprotective Agents / pharmacology*
  • Pitch Perception / drug effects*
  • Pseudomonas aeruginosa Exotoxin A
  • Round Window, Ear / drug effects
  • Virulence Factors / toxicity*

Substances

  • Bacterial Toxins
  • Brain-Derived Neurotrophic Factor
  • Exotoxins
  • Neuroprotective Agents
  • Virulence Factors
  • ADP Ribose Transferases
  • NG-Nitroarginine Methyl Ester