Escherichia coli 0111 B4 lipopolysaccharide given intracisternally induces blood-brain barrier opening during experimental neonatal meningitis in piglets.
Neonatal bacterial meningitis remains a life-threatening infection, and severe neurologic sequelae may be left in survivors as well. The goal of the study was to develop and characterize a porcine model of the disease with intravital observation of the permeability changes in cerebral microvessels. Eighteen newborn piglets were given doses of 0 ng (group 1), 20 ng (group 2), and 200 ng (group 3) of Escherichia coli 0111 B4 endotoxin (LPS) intracisternally (n = 6 in each group). Cardiovascular parameters were without changes, but a compensated metabolic acidosis occurred in group 3 4 h after LPS injection. Using the open cranial window technique combined with fluorescence excitation, there was no blood-brain barrier leakage in pial-arachnoid microvessels for sodium fluorescein during the 4 h of experiments in group 1 piglets, whereas spotty extravasations occurred in group 2 and in group 3 after the LPS injections (70.5 +/- 10.5 and 55.2 +/- 4.1 min, respectively, mean +/- SEM). A dose-dependent increase in sodium fluorescein uptake in brain regions examined (parietal and occipital cortex, cerebellum, and periventricular white matter) was also found by fluorescence spectrophotometry. LPS-treated piglets had developed pleocytosis. Four h after the challenge, the white blood cell counts in cerebrospinal fluid were (mean +/- SD): group 1, 8.2 +/- 7.6 microL-1; group 2, 453 +/- 703 microL-1; and group 3, 1 027 +/- 620 microL-1, respectively, whereas there was no change in white blood cell count of peripheral blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)
Temesvári
P
P
Department of Pediatrics, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Abrahám
C S
CS
Speer
C P
CP
Kovács
J
J
Megyeri
P
P
D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D016920:Meningitis, Bacterial / Q000209:etiology* / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects / Q000503:physiopathology; D008856:Microscopy, Fluorescence; D010539:Permeability; D012969:Sodium Fluoride / Q000493:pharmacokinetics; D014018:Tissue Distribution
D008070:Lipopolysaccharides; D012969:Sodium Fluoride