Document Detail


Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury.
MedLine Citation:
PMID:  23281396     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oligodendrocyte precursor cells (OPCs) are thought to maintain homeostasis and contribute to long-term repair in adult white matter; however, their roles in the acute phase after brain injury remain unclear. Mice that were subjected to prolonged cerebral hypoperfusion stress developed white matter demyelination over time. Prior to demyelination, we detected increased MMP9 expression, blood-brain barrier (BBB) leakage, and neutrophil infiltration in damaged white matter. Notably, at this early stage, OPCs made up the majority of MMP9-expressing cells. The standard MMP inhibitor GM6001 reduced the early BBB leakage and neutrophil infiltration, indicating that OPC-derived MMP9 induced early BBB disruption after white matter injury. Cell-culture experiments confirmed that OPCs secreted MMP9 under pathological conditions, and conditioned medium prepared from the stressed OPCs weakened endothelial barrier tightness in vitro. Our study reveals that OPCs can rapidly respond to white matter injury and produce MMP9 that disrupts the BBB, indicating that OPCs may mediate injury in white matter under disease conditions.
Authors:
Ji Hae Seo; Nobukazu Miyamoto; Kazuhide Hayakawa; Loc-Duyen D Pham; Takakuni Maki; Cenk Ayata; Kyu-Won Kim; Eng H Lo; Ken Arai
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-02
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2013-05-13     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  782-6     Citation Subset:  AIM; IM    
Affiliation:
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / pathology,  physiology
Animals
Blood-Brain Barrier / drug effects,  pathology*,  physiopathology*
Brain Injuries / pathology*,  physiopathology*
Dipeptides / pharmacology
Disease Models, Animal
Male
Matrix Metalloproteinase 9 / biosynthesis
Matrix Metalloproteinases, Secreted / antagonists & inhibitors
Mice
Mice, Inbred C57BL
Neural Stem Cells / pathology,  physiology
Neutrophil Infiltration / drug effects,  physiology
Oligodendroglia / pathology*,  physiology*
Protease Inhibitors / pharmacology
Grant Support
ID/Acronym/Agency:
R01 NS065089/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Dipeptides; 0/N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; 0/Protease Inhibitors; EC 3.4.24.-/Matrix Metalloproteinases, Secreted; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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