title: Adjunctive N-acetyl-L-cysteine in treatment of murine pneumococcal meningitis.
abstract: Despite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment with N-acetyl-l-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are limited. Here, we investigated the impact of adjunctive N-acetyl-l-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected with Streptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone and N-acetyl-l-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. Adjunctive N-acetyl-l-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctive N-acetyl-l-cysteine treatment in regard to other long-term complications of pneumococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-l-cysteine. In conclusion, adjunctive therapy with N-acetyl-l-cysteine at a dosage of 300 mg/kg of body weight intraperitoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These results make a clinical therapeutic benefit of N-acetyl-l-cysteine in the treatment of patients with pneumococcal meningitis questionable.
authors.affiliation: Department of Neurology, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Högen
authors.forename: Cornelia
authors.initials: C
authors.lastname: Demel
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Barbara
authors.initials: B
authors.lastname: Angele
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Pfister
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry* / Q000627:therapeutic use*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use; D003051:Cochlea / Q000382:microbiology; D004195:Disease Models, Animal; D034381:Hearing Loss / Q000188:drug therapy; D008297:Male; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D000111:Acetylcysteine