Escherichia coli o111 B4 lipopolysaccharide given intracisternallyinduces 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 µL-1; group 2, 453 ± 703 µL-1; and group 3,1 027 ± 620 µL-1, respectively, whereas there was no change in white blood cell count of peripheral blood samples. Sixty min after the intracisternal injection, LPS content measured by Limulus amebocytes lysate assay was mildly elevated in cerebrospinal fluid in group 2 and group 3, whereas it was unchanged in sera in either group. We conclude that our model may be appropriate for further in vivo examination of the pathogenesis and treatment of neonatal bacterial meningitis. © 1993 International Pediatric Research Foundation, Inc.