A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease

The course of bacterial titers, meningeal inflammation, behavioral abnormal ities, and neuronal damage was studied in a mouse model of Streptococcus pn eumoniae 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 neuron al 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 th at in wild-type litrermates. 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 fur therapeutic studies and for the inv estigation of inflammation in knockout mice. The neuronal damage resembles morphological abnormalities observed in humans.