Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis: Journal of Infectious Diseases

C.T. Brandt, D. Holm, Matthew George Liptrot, C. Østergaard, J.D. Lundgren, N. Frimodt-Møller, I.C. Skovsted, I.J. Rowland

23 Citations (Scopus)

Abstract

Background. Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain. Methods. Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study rats: (1) rats with attenuated bacteremia resulting from intravenous injection of serotype-specific pneumococcal antibody, (2) rats with early-onset bacteremia resulting from concomitant intravenous infection, or (3) a meningitis control group. The blood-brain barrier (BBB) breakdown, ventricle size, brain water distribution, and brain pathologic findings were analyzed using magnetic resonance morphological and functional imaging. Laboratory data and clinical disease scores were obtained. Results. Attenuation of the bacteremic component of pneumococcal meningitis improved clinical disease symptoms and significantly reduced ventricle expansion and BBB breakdown (P <.05). Early-onset bacteremia did not further increase ventricle size or BBB leakage. Significantly increased brain edema developed among rats with both attenuated and early-onset bacteremia (P <.05). Focal brain pathologic findings were unaffected by bacteremia and were found to be associated with cerebrospinal fluid inflammation. Conclusion. Although brain lesions appear to result from local meningeal infection, systemic infection significantly contributes to clinical disease presentation and the pathophysiology of BBB breakdown and ventricle expansion. The different end points affected by the systemic and local infectious processes should be addressed in future studies. © 2008 by the Infectious Diseases Society of America. All rights reserved.
Original languageEnglish
JournalJ. Infect. Dis.
Volume197
Issue number2
Pages (from-to)235-244
Number of pages10
ISSN0022-1899
DOIs
Publication statusPublished - 2008

Keywords

  • antibody
  • pneumococcal antibody
  • unclassified drug
  • animal experiment
  • animal model
  • animal tissue
  • article
  • bacteremia
  • bacterial meningitis
  • blood brain barrier
  • brain
  • brain edema
  • brain ventricle
  • cerebrospinal fluid
  • concurrent infection
  • controlled study
  • experimental infection
  • laboratory test
  • male
  • nonhuman
  • nuclear magnetic resonance
  • pathogenesis
  • priority journal
  • rat
  • serotyping
  • statistical significance
  • animal
  • blood
  • hospitalization
  • human
  • immunology
  • inflammation
  • isolation and purification
  • microbiology
  • motor performance
  • nuclear magnetic resonance imaging
  • pathogenicity
  • pathology
  • pathophysiology
  • Streptococcus pneumoniae
  • Wistar rat
  • Animals
  • Bacteremia
  • Blood
  • Blood-Brain Barrier
  • Brain
  • Brain Edema
  • Cerebrospinal Fluid
  • Humans
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Meningitis, Pneumococcal
  • Motor Skills
  • Rats
  • Rats, Wistar
  • Severity of Illness Index

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