Pharmacologic interference with NF-kappaB activation attenuates central nervous system complications in experimental Pneumococcal meningitis - PubMed (original) (raw)

. 2000 Nov;182(5):1437-45.

doi: 10.1086/315877. Epub 2000 Oct 9.

Affiliations

• PMID: 11023466
• DOI: 10.1086/315877

Pharmacologic interference with NF-kappaB activation attenuates central nervous system complications in experimental Pneumococcal meningitis

U Koedel et al. J Infect Dis. 2000 Nov.

Abstract

This study assessed the effects of 2 different inhibitors of NF-kappaB activation on central nervous system complications and clinical symptoms in an advanced stage of experimental pneumococcal meningitis: the calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which interferes with IkappaB proteolysis, and BAY 11-7085, which inhibits IkappaB phosphorylation. Pneumococcal meningitis was associated with an increase in NF-kappaB activity, as determined by immunohistochemistry and Western blot analysis of rat brains 24 h after infection. Treatment with ALLN or BAY 11-7085 improved the clinical scores of infected rats, compared with those of untreated infected rats. This beneficial effect was parallelled by a significant reduction of the increase in intracranial pressure, blood-brain barrier permeability (as measured by the Evans blue-extravasation technique), cerebrospinal fluid (CSF) pleocytosis, CSF interleukin-6 levels, and impairment of cerebrovascular CO(2) reactivity and autoregulation. Thus, pharmacologic interference with NF-kappaB activation might be a possible target for adjunctive therapy in bacterial meningitis.

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