Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis.

Christian T Brandt; David Holm; Matthew Liptrot; Christian Ostergaard; Jens D Lundgren; Niels Frimodt-Møller; Ian C Skovsted; Ian J Rowland

doi:10.1086/524874

Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis.

Christian T Brandt, David Holm, Matthew Liptrot, Christian Ostergaard, Jens D Lundgren, Niels Frimodt-Møller, Ian C Skovsted, Ian 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.
Udgivelsesdato: 2008-Jan-15

Original language	English
Journal	Journal of Infectious Diseases
Volume	197
Issue number	2
Pages (from-to)	235-44
Number of pages	9
ISSN	0022-1899
DOIs	https://doi.org/10.1086/524874 https://doi.org/10.1086/524874
Publication status	Published - 2008

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@article{c102d530ff3911ddb219000ea68e967b,

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. 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. Udgivelsesdato: 2008-Jan-15",

author = "Brandt, {Christian T} and David Holm and Matthew Liptrot and Christian Ostergaard and Lundgren, {Jens D} and Niels Frimodt-M{\o}ller and Skovsted, {Ian C} and Rowland, {Ian J}",

note = "Keywords: 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; Streptococcus pneumoniae",

year = "2008",

doi = "10.1086/524874",

language = "English",

volume = "197",

pages = "235--44",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis.

AU - Brandt, Christian T

AU - Holm, David

AU - Liptrot, Matthew

AU - Ostergaard, Christian

AU - Lundgren, Jens D

AU - Frimodt-Møller, Niels

AU - Skovsted, Ian C

AU - Rowland, Ian J

N1 - Keywords: 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; Streptococcus pneumoniae

PY - 2008

Y1 - 2008

N2 - 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. Udgivelsesdato: 2008-Jan-15

AB - 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. Udgivelsesdato: 2008-Jan-15

U2 - 10.1086/524874

DO - 10.1086/524874

M3 - Journal article

C2 - 18173365

SN - 0022-1899

VL - 197

SP - 235

EP - 244

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 2

ER -