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.
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Authors | Matthias Klein, Uwe Koedel, Hans-Walter Pfister, Stefan Kastenbauer |
Journal | Annals of neurology
(Ann Neurol)
Vol. 54
Issue 4
Pg. 451-8
(Oct 2003)
ISSN: 0364-5134 [Print] United States |
PMID | 14520656
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Bacterial Agents
- Antioxidants
- Metalloporphyrins
- manganese(III)-tetrakis(4-benzoic acid)porphyrin
- Peroxynitrous Acid
- Evans Blue
- Ceftriaxone
- Acetylcysteine
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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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