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PMID: 3262627 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 82 ·No. 4 ·1988-10-00 ·Pages 1339-46

Wispelwey B, Lesse AJ, Hansen EJ, Scheld WM

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 microgram; (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.

MeSH Terms
Animals Bacterial Vaccines/toxicity Blood-Brain Barrier/drug effects Capillary Permeability/drug effects Dose-Response Relationship, Drug Haemophilus influenzae/analysis Kinetics Leukopenia/physiopathology Lipopolysaccharides/toxicity Meningitis/etiology,physiopathology Rats Rats, Inbred Strains
Chemicals
Bacterial Vaccines Lipopolysaccharides
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wispelwey B
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Lesse A J
Hansen E J
Scheld W M
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI113736
Published
1988-10-00
Pages
1339-46
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC442689
Subset
IM
Grants
NIAID NIH HHS · AI 17904 · United States
NIAID NIH HHS · T 32-AI07046 · United States
External Links
PubMed source DOI: 10.1172/JCI113736 PMC Full Text View journal details
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