Meningitis-associated hearing loss: protection by adjunctive antioxidant therapy.
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.
Klein
Matthias
M
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Koedel
Uwe
U
Pfister
Hans-Walter
HW
Kastenbauer
Stefan
S
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D001299:Audiometry; D002443:Ceftriaxone / Q000627:therapeutic use; D002452:Cell Count / Q000379:methods; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D005070:Evans Blue / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D034381:Hearing Loss / Q000209:etiology / Q000517:prevention & control*; D007762:Labyrinthitis / Q000382:microbiology / Q000473:pathology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000150:complications* / Q000382:microbiology; D008665:Metalloporphyrins / Q000627:therapeutic use; D030421:Peroxynitrous Acid / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D008665:Metalloporphyrins; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D030421:Peroxynitrous Acid; D005070:Evans Blue; D002443:Ceftriaxone; D000111:Acetylcysteine