A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease.
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.
Gerber
J
J
Department of Neurology, University of Göttingen, Germany.
Raivich
G
G
Wellmer
A
A
Noeske
C
C
Kunst
T
T
Werner
A
A
Brück
W
W
Nau
R
R
D000818:Animals; D001835:Body Weight / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D015996:Survival Rate; D016896:Treatment Outcome
D002511:Cephalosporins; D005904:Glial Fibrillary Acidic Protein; D018960:Hyaluronan Receptors; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D002443:Ceftriaxone; D016173:Macrophage Colony-Stimulating Factor