Abstract
The course of bacterial titers, meningeal inflammation, behavioral abnormalities, and neuronal damage was studied in a mouse model of Streptococcus pneumoniae meningitis. At 24 h after injection of 10(4) colony-forming units (CFU) S. pneumoniae into the right forebrain, infected mice became severely lethargic. Bacterial titers in cerebrospinal fluid and cerebellum rose to 10(9) CFU/ml, with strong granulocyte invasion into the meninges and neuronal necroses in the neocortex, striatum and hippocampal formation. Meningeal inflammation and neuronal damage in intercellular cell adhesion molecule-1- and macrophage colony-stimulating factor-deficient mice was similar to that in wild-type littermates. Untreated, the infection was fatal. Wild-type mice treated earlier than 24 h after infection with ceftriaxone (2 mg every 12 h for 3 days) survived without apparent behavioral abnormalities. Delay of treatment beyond 30 h led to the death of more than 50% of the infected mice. This mouse model is suitable for therapeutic studies and for the investigation of inflammation in knockout mice. The neuronal damage resembles morphological abnormalities observed in humans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Body Weight / immunology
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Brain / immunology
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Brain / microbiology*
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Brain / pathology*
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Ceftriaxone / pharmacology
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Cephalosporins / pharmacology
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Disease Models, Animal*
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Glial Fibrillary Acidic Protein / metabolism
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Gliosis / immunology
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Gliosis / microbiology
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Gliosis / pathology
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Hyaluronan Receptors / metabolism
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Immunohistochemistry
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Leukocyte Count
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Leukocytes / immunology
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Leukocytes / microbiology
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Leukocytes / pathology
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Macrophage Colony-Stimulating Factor / deficiency
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Macrophage Colony-Stimulating Factor / genetics
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Macrophage-1 Antigen / metabolism
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Meningitis, Pneumococcal / drug therapy
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Meningitis, Pneumococcal / pathology*
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Meningitis, Pneumococcal / physiopathology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Streptococcus pneumoniae / drug effects
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Streptococcus pneumoniae / pathogenicity*
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Streptococcus pneumoniae / physiology
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Survival Rate
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Treatment Outcome
Substances
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Cephalosporins
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Glial Fibrillary Acidic Protein
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Hyaluronan Receptors
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Macrophage-1 Antigen
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Intercellular Adhesion Molecule-1
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Ceftriaxone
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Macrophage Colony-Stimulating Factor