title: Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Center for Antimicrobials and Infection Control, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. ctb@ssi.dk
authors.forename: Christian T
authors.initials: CT
authors.lastname: Brandt
authors.forename: David
authors.initials: D
authors.lastname: Holm
authors.forename: Matthew
authors.initials: M
authors.lastname: Liptrot
authors.forename: Christian
authors.initials: C
authors.lastname: Ostergaard
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: Ian C
authors.initials: IC
authors.lastname: Skovsted
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Rowland
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology; D001769:Blood / Q000382:microbiology; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000382:microbiology / Q000473:pathology; D001929:Brain Edema / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000382:microbiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D009048:Motor Skills; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000302:isolation & purification / Q000472:pathogenicity