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  • Title: Pneumococcal meningitis in the rat: evaluation of peroxynitrite scavengers for adjunctive therapy.
    Author: Kastenbauer S, Koedel U, Becker BF, Pfister HW.
    Journal: Eur J Pharmacol; 2002 Aug 02; 449(1-2):177-81. PubMed ID: 12163122.
    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).
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