Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat

B. Wispelwey, A. J. Lesse, E. J. Hansen, W. M. Scheld

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Abstract

The factors responsible for blood-brain barrier (BBB) injury during bacterial meningitis are incompletely defined. We evaluated the role of Haemophilus influenzae type b (Hib) lipopolysaccharide (LPS) in the alteration of blood-brain barrier permeability (BBBP) in an adult, normal and leukopenic, rat model of meningitis. Intracisternal inoculation of Hib LPS resulted in (a) dose-dependent increases in BBBP from 2 pg to 20 ng, with significant attenuation in the peak response after challenge with 500 ng and 1 μg; (b) time-dependent increases in BBBP, with a delayed onset of at least 2 h, maximum alteration at 4 h, and complete reversal at 18 h; (c) greater BBBP than after challenge with the live parent strain; (d) and a close correlation (r = 0.86) between CSF pleocytosis and BBBP at 4 h. The LPS effect was significantly inhibited by preincubation with Polymyxin B and neutrophil acyloxyacyl hydrolase, however two different oligosaccharide-specific monoclonal antibodies did not inhibit activity. No change in BBBP after inoculation with Hib LPS occurred in leukopenic rats. Hib LPS, in the setting of an intact leukocyte response, exerts profound effects on BBBP.

Original languageEnglish (US)
Pages (from-to)1339-1346
Number of pages8
JournalJournal of Clinical Investigation
Volume82
Issue number4
StatePublished - 1988

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Haemophilus influenzae
Blood-Brain Barrier
Meningitis
Lipopolysaccharides
Permeability
Haemophilus influenzae type b
Polymyxin B
Bacterial Meningitides
Leukocytosis
Oligosaccharides
Brain Injuries
Neutrophils
Leukocytes
Monoclonal Antibodies

ASJC Scopus subject areas

  • Medicine(all)

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Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. / Wispelwey, B.; Lesse, A. J.; Hansen, E. J.; Scheld, W. M.

In: Journal of Clinical Investigation, Vol. 82, No. 4, 1988, p. 1339-1346.

Research output: Contribution to journalArticle

Wispelwey, B. ; Lesse, A. J. ; Hansen, E. J. ; Scheld, W. M. / Haemophilus influenzae lipopolysaccharide-induced blood brain barrier permeability during experimental meningitis in the rat. In: Journal of Clinical Investigation. 1988 ; Vol. 82, No. 4. pp. 1339-1346.
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