Escherichia coli 0111 B4 lipopolysaccharide given intracisternally induces blood-brain barrier opening during experimental neonatal meningitis in piglets.

Abstract

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)

• Authors: P Temesvári, C S Abrahám, C P Speer, J Kovács, P Megyeri
• Journal: Pediatric research (Pediatr Res) Vol. 34 Issue 2 Pg. 182-6 (Aug 1993) ISSN: 0031-3998 [Print] United States
• PMID: 8233723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Sodium Fluoride

Topics

• Animals
• Animals, Newborn
• Blood-Brain Barrier (drug effects, physiology)
• Disease Models, Animal
• Escherichia coli Infections (etiology, physiopathology)
• Female
• Injections, Intraventricular
• Lipopolysaccharides (administration & dosage, toxicity)
• Male
• Meningitis, Bacterial (etiology, physiopathology)
• Microcirculation (drug effects, physiopathology)
• Microscopy, Fluorescence
• Permeability
• Sodium Fluoride (pharmacokinetics)
• Tissue Distribution