Increased mortality and spatial memory deficits in TNF-alpha-deficient mice in ceftriaxone-treated experimental pneumococcal meningitis.
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.
Gerber
Joachim
J
Department of Neurology, Georg-August-University, Göttingen 37075, Germany.
Böttcher
Tobias
T
Hahn
Michael
M
Siemer
Alexander
A
Bunkowski
Stephanie
S
Nau
Roland
R
D000818:Animals; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone