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The NR1 subunit of NMDA receptor regulates monocyte transmigration through the brain endothelial cell barrier
Author(s) -
Reijerkerk Arie,
Kooij Gijs,
Van Der Pol Susanne M. A.,
Leyen Thomas,
Lakeman Kim,
Van Het Hof Bert,
Vivien Denis,
De Vries Helga E.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06598.x
Subject(s) - blood–brain barrier , endothelial stem cell , microbiology and biotechnology , biology , inflammation , plasminogen activator , endothelium , cell type , neuroinflammation , receptor , immunology , neuroscience , cell , central nervous system , endocrinology , biochemistry , in vitro
J. Neurochem. (2010) 113 , 447–453. Abstract Normal neuronal functioning is dependent on the blood‐brain barrier. This barrier is confined to specialized brain endothelial cells lining the inner vessel wall, and tightly controlling transport of nutrients, efflux of potentially harmful molecules and entry of immune cells into the brain. Loss of blood‐brain barrier function is an early and significant event which contributes to inflammation in the brain and subsequent progression of neuronal deficits in a number of brain disorders and has been well‐documented for the auto‐immune disease multiple sclerosis. Extravasation of cells happens by paracellular transport across the endothelial junctions, transcellularly across the endothelial cells, or both, and requires the active participation of endothelial cells. We and others have shown that this process requires the activity of proteases, including tissue‐type plasminogen activator. We here describe a novel role for NMDA receptor, a potential cellular target of tissue‐type plasminogen activator, in human brain endothelial cells. Our results show that the NMDA receptor subunit 1 (NR1) is expressed in brain endothelial cells, regulates tissue‐type plasminogen activator‐induced signal transduction and controls the passage of monocytes through the brain endothelial cell barrier. Together, our results hold significant promise for the treatment of chronic inflammation in the brain.