title: Pneumococcal meningitis in the rat: evaluation of peroxynitrite scavengers for adjunctive therapy.
abstract: We evaluated the effect of different peroxynitrite scavengers for adjunctive therapy of experimental bacterial meningitis. Twenty hours after intracisternal injection of Streptococcus pneumoniae, rats were treated with ceftriaxone [100 mg/kg intraperitoneal (i.p.)] and either urate (300 mg/kg i.p.), Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP, 15 mg/kg i.p.), ascorbate (100 mg/kg i.p.), or urate (300 mg/kg i.p.) + ascorbate (100 mg/kg i.p.). Six hours after initiation of treatment, the cerebrospinal fluid (CSF) pleocytosis was significantly (p<0.05) reduced by urate (8697 +/- 1526 cells/microl) and MnTBAP (8542 +/- 4059 cells/microl) vs. ceftriaxone alone (15,793 +/- 3202 cells/microl). Brain concentrations of proinflammatory cytokines [interleukin-1beta (IL-beta), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2)] were also reduced by urate and MnTBAP. The intracranial hypertension was significantly reduced by MnTBAP (14.0 +/- 5.4 mm Hg), but not by urate (25.5 +/- 7.1 mm Hg) vs. ceftriaxone alone (22.5 +/- 5.9 mm Hg). Ascorbate alone had no effect on CSF pleocytosis (15,775 +/- 7058 cells/microl), intracranial pressure (25.6 +/- 8.8 mm Hg), and brain cytokine concentrations. However, the combination of urate and ascorbate was as effective as MnTBAP (CSF pleocytosis: 5392 +/- 4232 cells/microl, intracranial pressure: 13.3 +/- 6.9 mm Hg).
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kastenbauer
authors.forename: U
authors.initials: U
authors.lastname: Koedel
authors.forename: B F
authors.initials: BF
authors.lastname: Becker
authors.forename: H W
authors.initials: HW
authors.lastname: Pfister
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002443:Ceftriaxone / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000382:microbiology; D015846:Monokines / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002511:Cephalosporins; D054426:Chemokine CXCL2; D018925:Chemokines; D016207:Cytokines; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D007375:Interleukin-1; D015850:Interleukin-6; D015846:Monokines; D030421:Peroxynitrous Acid; D002443:Ceftriaxone