Source:http://linkedlifedata.com/resource/pubmed/id/18996441
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2008-12-16
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| pubmed:abstractText |
The aim of the present study was to examine the signaling pathways of hypoxia followed by reoxygenation (H/R)-induced disruption of the blood-brain-barrier (BBB) in a co-culture of astrocytes and brain endothelial cells (BEC) in vitro. We analyzed the possible stabilizing effect of MK801, a highly selective N-methyl-d-aspartate receptor (NMDAR) antagonist, on BBB integrity. Levels of reactive oxygen species (ROS), glutamate (Glut) release and monocyte adhesion were measured under normoxia and H/R. BBB integrity was monitored measuring the trans-endothelial electrical resistance (TEER). TEER values dropped under H/R conditions which was abolished by MK801. Glut release from astrocytes, but not from endothelial cells was significantly increased under H/R, as were ROS levels and monocyte adhesion. The oxidative stress was blocked by MK801 and the NAD(P)H-oxidase inhibitor apocynin. We observed that calcium (Ca(2+)) signaling plays a crucial role during ROS generation and monocyte adhesion under H/R. ROS levels were decreased by applying ryanodine, a blocker of Ca(2+) release from the endoplasmic reticulum (ER) and by lowering the extracellular Ca(2+) concentration. Xestospongin C, which blocks IP(3) mediated Ca(2+) release from the ER did not alter ROS production under H/R conditions. These findings indicate that both extracellular Ca(2+) influx and ryanodine-mediated intracellular Ca(2+) release from the ER during H/R contribute to ROS formation at the BBB. Blocking ROS or Ca(2+) signaling prevented H/R-induced monocyte adhesion to BEC. We conclude, that the activation of NMDAR under H/R by Glut increases intracellular Ca(2+) levels, contributes to BBB disruption, ROS generation and monocyte adhesion.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetophenones,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Macrocyclic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Oxazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine,
http://linkedlifedata.com/resource/pubmed/chemical/acetovanillone,
http://linkedlifedata.com/resource/pubmed/chemical/xestospongin C
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0304-3940
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
16
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| pubmed:volume |
449
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
168-72
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| pubmed:meshHeading |
pubmed-meshheading:18996441-Acetophenones,
pubmed-meshheading:18996441-Animals,
pubmed-meshheading:18996441-Astrocytes,
pubmed-meshheading:18996441-Blood-Brain Barrier,
pubmed-meshheading:18996441-Brain,
pubmed-meshheading:18996441-Calcium,
pubmed-meshheading:18996441-Cell Adhesion,
pubmed-meshheading:18996441-Cell Hypoxia,
pubmed-meshheading:18996441-Cells, Cultured,
pubmed-meshheading:18996441-Coculture Techniques,
pubmed-meshheading:18996441-Dizocilpine Maleate,
pubmed-meshheading:18996441-Electric Impedance,
pubmed-meshheading:18996441-Endothelial Cells,
pubmed-meshheading:18996441-Enzyme Inhibitors,
pubmed-meshheading:18996441-Excitatory Amino Acid Antagonists,
pubmed-meshheading:18996441-Glutamic Acid,
pubmed-meshheading:18996441-Leukocytes,
pubmed-meshheading:18996441-Macrocyclic Compounds,
pubmed-meshheading:18996441-Oxazoles,
pubmed-meshheading:18996441-Oxygen,
pubmed-meshheading:18996441-Reactive Oxygen Species,
pubmed-meshheading:18996441-Ryanodine,
pubmed-meshheading:18996441-Swine
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| pubmed:year |
2009
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| pubmed:articleTitle |
MK801 blocks hypoxic blood-brain-barrier disruption and leukocyte adhesion.
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| pubmed:affiliation |
Institute of Physiology and Pathophysiology, Johannes Gutenberg University of Mainz, Duesbergweg 6, 55128 Mainz, Germany. SuC.Kuhlmann@t-online.de
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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