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Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat.
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MedLine Citation:
PMID:  1875166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Injury to the blood brain barrier (BBB) is a fundamental sequela of bacterial meningitis, yet the precise mechanism facilitating exudation of albumin across the endothelium of the cerebral microvasculature remains conjectural. After intracisternal inoculation of Escherichia coli (0111:B4) lipopolysaccharide in rats to elicit a reversible meningitis and BBB injury, we utilized in situ tracer perfusion and immunolabeling procedures to identify by transmission electron microscopy the precise topography and microvascular exit pathway(s) of bovine serum albumin (BSA). Results revealed that during meningitis there was: (a) an inducible increase in immunodetectable monomeric BSA binding to the luminal membrane of all microvascular segments in the pia-arachnoid and superficial brain cortex; (b) similar uptake of both colloidal Au-BSA (as well as monomeric BSA) by plasmalemmal vesicles but no detectable transcytosis to the abluminal side; and (c) predominant exit of both perfused Au-BSA and immunodetectable monomeric BSA through open intercellular junctions of venules in the pia-arachnoid. This was corroborated in separate experiments documenting focal pial venular leaks of in situ perfused 0.01% colloidal carbon black during experimental meningitis. These results provide precise localization of BBB injury in meningitis to meningeal venules, confirm a paracellular exit pathway of albumin via open intercellular junctions, and suggest an injury mechanism amenable to specific therapeutic intervention.
Authors:
V J Quagliarello; A Ma; H Stukenbrok; G E Palade
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of experimental medicine     Volume:  174     ISSN:  0022-1007     ISO Abbreviation:  J. Exp. Med.     Publication Date:  1991 Sep 
Date Detail:
Created Date:  1991-09-26     Completed Date:  1991-09-26     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985109R     Medline TA:  J Exp Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  657-72     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Blood-Brain Barrier*
Carbon
Escherichia coli
Immunohistochemistry
Lipopolysaccharides / administration & dosage
Male
Meningitis / metabolism*,  pathology
Microcirculation / metabolism*
Rats
Rats, Inbred Strains
Serum Albumin, Bovine / metabolism*
Grant Support
ID/Acronym/Agency:
5-K11-HL02062-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Serum Albumin, Bovine; 7440-44-0/Carbon
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Exp Med
ISSN: 0022-1007
ISSN: 1540-9538
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 1 Month: 9 Year: 1991
Volume: 174 Issue: 3
First Page: 657 Last Page: 672
ID: 2118932
Publisher Id: 91341426
PubMed Id: 1875166

Ultrastructural localization of albumin transport across the cerebral microvasculature during experimental meningitis in the rat


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