Tumor necrosis factor alpha (TNF-alpha) levels in the brain and cerebrospinal fluid after meningitis induced by Streptococcus pneumoniae

Neurosci Lett. 2009 Dec 31;467(3):217-9. doi: 10.1016/j.neulet.2009.10.039. Epub 2009 Oct 14.


Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process include tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6. TNF-alpha have several effects, including cytotoxicity, antiviral activity, transcription factor activation, and immune response regulation. Thus, the aim of this study was to verify the levels of the TNF-alpha after pneumococcal meningitis in male Wistar rats. The animals underwent a magna cistern tap receiving either 10 microL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 5 x 10(9)cfu/mL. The animals were killed at 0, 6, 12, 24, 48 and 96 h after induction. The brain was removed and hippocampus, cortex, prefrontal and cerebrospinal fluid (CSF) were isolated and used for the determination of TNF-alpha levels. We found an increase in TNF-alpha levels at 6h after induction of the meningitis in the hippocampus (p<0.01), frontal cortex (p<0.05), and cerebrospinal fluid (p<0.001).There was no alteration in the cortex. Our data suggest that TNF-alpha is involved in the pathophysiology of the pneumococcal meningitis and could be investigated as a putative biomarker for brain damage in the first hours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid
  • Brain / immunology*
  • Brain / physiopathology
  • Cerebrospinal Fluid / immunology
  • Cerebrospinal Fluid / metabolism
  • Cerebrospinal Fluid / microbiology
  • Diagnosis, Differential
  • Disease Models, Animal
  • Frontal Lobe / immunology
  • Frontal Lobe / physiopathology
  • Hippocampus / immunology
  • Hippocampus / physiopathology
  • Male
  • Meninges / immunology
  • Meninges / microbiology
  • Meninges / pathology
  • Meningitis, Pneumococcal / cerebrospinal fluid*
  • Meningitis, Pneumococcal / immunology*
  • Meningitis, Pneumococcal / physiopathology
  • Predictive Value of Tests
  • Rats
  • Streptococcal Infections / cerebrospinal fluid*
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / physiopathology
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / cerebrospinal fluid*
  • Up-Regulation / immunology


  • Biomarkers
  • Tumor Necrosis Factor-alpha