Related Experiment Video
Updated: Aug 23, 2026
Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Increased mortality and spatial memory deficits in TNF-alpha-deficient mice in ceftriaxone-treated experimental
Joachim Gerber1, Tobias Böttcher, Michael Hahn
1Department of Neurology, Georg-August-University, Göttingen 37075, Germany.
Abstract:
Tumor necrosis factor-alpha (TNF-alpha) is critically involved in inflammation and may participate in hippocampal injury in bacterial meningitis. In a mouse model of ceftriaxone-treated pneumococcal meningitis, spatial memory and motor performance of TNF-alpha-deficient (n = 57) and control mice (n = 55) were investigated. After infection, therapy was initiated with ceftriaxone (100 mg/kg twice daily for 5 days). Sixty-three percent TNF-alpha-deficient mice and 40% control animals died within 6 days (Fisher's exact test: P = 0.02). TNF-alpha-deficient mice surviving pneumococcal meningitis took substantially longer to reach the hidden platform than controls, and the distance of swim tracks was longer (P = 0.02). The swim speed in both groups was similar (P = 0.59). The proliferation of dentate granule cells was lower in TNF-alpha-deficient than in wild-type mice (P = 0.03). In pneumococcal meningitis, TNF-alpha deficiency caused increased mortality and stronger deficits in spatial memory possibly due to impaired neurogenesis.
Insights
Tumor necrosis factor-alpha (TNF-alpha) deficiency increased mortality and spatial memory deficits in pneumococcal meningitis. Impaired neurogenesis may contribute to these negative outcomes in mice.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Tumor necrosis factor-alpha (TNF-alpha) plays a key role in inflammation.
- TNF-alpha may contribute to hippocampal injury during bacterial meningitis.
Purpose of the Study:
- To investigate the role of TNF-alpha in pneumococcal meningitis.
- To assess the impact of TNF-alpha deficiency on spatial memory, motor performance, and survival in a mouse model.
Main Methods:
- A mouse model of ceftriaxone-treated pneumococcal meningitis was used.
- TNF-alpha-deficient and control mice were compared for survival rates, spatial memory (hidden platform task), and neurogenesis (dentate granule cell proliferation).
Main Results:
- TNF-alpha-deficient mice exhibited higher mortality rates (63%) compared to controls (40%).
- Surviving TNF-alpha-deficient mice showed significant deficits in spatial memory, taking longer to find the hidden platform.
- Dentate granule cell proliferation was reduced in TNF-alpha-deficient mice, suggesting impaired neurogenesis.
Conclusions:
- TNF-alpha deficiency exacerbates mortality and spatial memory impairments in pneumococcal meningitis.
- Impaired neurogenesis is a potential mechanism underlying the observed cognitive deficits in TNF-alpha-deficient mice.
