Document Detail

High-density lipoproteins limit neutrophil-induced damage to the blood-brain barrier in vitro.
MedLine Citation:
PMID:  23299241     Owner:  NLM     Status:  MEDLINE    
Breakdown of the blood-brain barrier (BBB) is a key step associated with ischemic stroke and its increased permeability causes extravasation of plasma proteins and circulating leukocytes. Polymorphonuclear neutrophil (PMN) proteases may participate in BBB breakdown. We investigated the role of PMNs in ischemic conditions by testing their effects on a model of BBB in vitro, under oxygen-glucose deprivation (OGD) to mimic ischemia, supplemented or not with high-density lipoproteins (HDLs) to assess their potential protective effects. Human cerebral endothelial cells cultured on transwells were incubated for 4 hours under OGD conditions with or without PMNs and supplemented or not with HDLs or alpha-1 antitrypsin (AAT, an elastase inhibitor). The integrity of the BBB was then assessed and the effect of HDLs on PMN-induced proteolysis of extracellular matrix proteins was evaluated. The release of myeloperoxidase and matrix metalloproteinase 9 (MMP-9) by PMNs was quantified. Polymorphonuclear neutrophils significantly increased BBB permeability under OGD conditions via proteolysis of extracellular matrix proteins. This was associated with PMN degranulation. Addition of HDLs or AAT limited the proteolysis and associated increased permeability by inhibiting PMN activation. Our results suggest a deleterious, elastase-mediated role of activated PMNs under OGD conditions leading to BBB disruption that could be inhibited by HDLs.
Quoc Bao Dang; Bertrand Lapergue; Alexy Tran-Dinh; Devy Diallo; Juan-Antonio Moreno; Mikael Mazighi; Ignacio A Romero; Babette Weksler; Jean-Baptiste Michel; Pierre Amarenco; Olivier Meilhac
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-09
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  575-82     Citation Subset:  IM    
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MeSH Terms
Blood-Brain Barrier / metabolism*,  pathology
Brain Ischemia / metabolism,  prevention & control*
Cell Line
Coculture Techniques
Endothelial Cells / metabolism*,  pathology
Extracellular Matrix Proteins / metabolism
Lipoproteins, HDL / pharmacology*
Matrix Metalloproteinase 9 / metabolism
Neutrophils / enzymology*,  pathology
Peroxidase / metabolism
Proteolysis / drug effects
Stroke / metabolism,  prevention & control*
Reg. No./Substance:
0/Extracellular Matrix Proteins; 0/Lipoproteins, HDL; EC; EC protein, human; EC Metalloproteinase 9

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