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Meningitis-associated hearing loss: protection by adjunctive antioxidant therapy.

Abstract
Hearing loss is the most frequent long-term complication of pneumococcal meningitis, affecting up to 40% of survivors. Unfortunately, adjuvant therapy with dexamethasone has failed to satisfactorily reduce its incidence. Therefore, we evaluated the use of antioxidants for the adjunctive therapy of meningitis-associated deafness. Eighteen hours after intracisternal injection of 7.5 x 10(5) colony-forming units of Streptococcus pneumoniae, rats were treated systemically either with ceftriaxone and the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-benzoic acid)-porphyrin (MnTBAP) or N-acetyl-L-cysteine (NAC) or placebo (1 ml phosphate-buffered saline) for 4 days. Hearing was assessed by auditory brainstem response audiometry. Adjunctive antioxidant therapy significantly reduced the long-term hearing loss (14 days after infection) for square wave impulses (mean hearing loss +/- SD: ceftriaxone and placebo, 45+/-26 dB; ceftriaxone and MnTBAP, 9+/-23 dB; ceftriaxone and NAC, 19+/-30 dB) as well as 1 kHz (ceftriaxone and placebo, 28+/-19 dB; ceftriaxone and MnTBAP, 10+/-16 dB; ceftriaxone and NAC, 10+/-17 dB), and 10 kHz tone bursts (ceftriaxone and placebo, 62+/-27 dB; ceftriaxone and MnTBAP, 16+/-13 dB; ceftriaxone and NAC, 25+/-26 dB). Furthermore, both antioxidants attenuated the morphological correlates of meningogenic hearing loss, namely, long-term blood-labyrinth barrier disruption, spiral ganglion neuronal loss, and fibrous obliteration of the perilymphatic spaces. Adjuvant antioxidant therapy is highly otoprotective in meningitis and therefore is a promising future treatment option.
AuthorsMatthias Klein, Uwe Koedel, Hans-Walter Pfister, Stefan Kastenbauer
JournalAnnals of neurology (Ann Neurol) Vol. 54 Issue 4 Pg. 451-8 (Oct 2003) ISSN: 0364-5134 [Print] United States
PMID14520656 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Antioxidants
  • Metalloporphyrins
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Peroxynitrous Acid
  • Evans Blue
  • Ceftriaxone
  • Acetylcysteine
Topics
  • Acetylcysteine (therapeutic use)
  • Animals
  • Anti-Bacterial Agents (therapeutic use)
  • Antioxidants (therapeutic use)
  • Audiometry
  • Ceftriaxone (therapeutic use)
  • Cell Count (methods)
  • Cochlea (drug effects, pathology)
  • Disease Models, Animal
  • Drug Interactions
  • Evans Blue (metabolism)
  • Evoked Potentials, Auditory, Brain Stem (physiology)
  • Hearing Loss (etiology, prevention & control)
  • Labyrinthitis (microbiology, pathology)
  • Male
  • Meningitis, Pneumococcal (complications, microbiology)
  • Metalloporphyrins (therapeutic use)
  • Peroxynitrous Acid (therapeutic use)
  • Rats
  • Rats, Wistar
  • Spiral Ganglion (drug effects, pathology)
  • Time Factors

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