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Updated: Sep 17, 2026
Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
A mouse model of Streptococcus pneumoniae meningitis mimicking several features of human disease
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.
Insights
Early ceftriaxone treatment saves mice from fatal Streptococcus pneumoniae meningitis. Prompt intervention prevents severe bacterial infection, inflammation, and neuronal damage, highlighting the importance of timely antibiotic therapy.
Area of Science:
- Neuroscience
- Infectious Diseases
- Immunology
Background:
- Streptococcus pneumoniae meningitis is a severe infection causing significant morbidity and mortality.
- Understanding the progression of meningitis and its neurological consequences is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the course of bacterial meningitis, inflammation, and neuronal damage in a mouse model.
- To evaluate the efficacy of ceftriaxone treatment at different time points post-infection.
Main Methods:
- Establishment of a mouse model by intracerebral injection of Streptococcus pneumoniae.
- Monitoring of bacterial titers, meningeal inflammation, behavioral changes, and neuronal damage.
- Assessment of treatment effects with ceftriaxone at various intervals.
Main Results:
- S. pneumoniae infection led to high bacterial titers, severe meningeal inflammation, and widespread neuronal damage.
- Intercellular cell adhesion molecule-1 and macrophage colony-stimulating factor deficiency did not alter disease severity.
- Early ceftriaxone treatment (before 24 hours) resulted in survival and absence of behavioral abnormalities.
- Delayed treatment (after 30 hours) led to over 50% mortality.
Conclusions:
- The developed mouse model accurately reflects human meningitis pathology and is suitable for therapeutic studies.
- Timely antibiotic intervention is critical for successful treatment outcomes in bacterial meningitis.
- The study underscores the importance of early diagnosis and treatment initiation for S. pneumoniae meningitis.
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