کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6285787 | 1296868 | 2009 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
MK801 blocks hypoxic blood-brain-barrier disruption and leukocyte adhesion
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
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 (Ca2+) signaling plays a crucial role during ROS generation and monocyte adhesion under H/R. ROS levels were decreased by applying ryanodine, a blocker of Ca2+ release from the endoplasmic reticulum (ER) and by lowering the extracellular Ca2+ concentration. Xestospongin C, which blocks IP3 mediated Ca2+ release from the ER did not alter ROS production under H/R conditions. These findings indicate that both extracellular Ca2+ influx and ryanodine-mediated intracellular Ca2+ release from the ER during H/R contribute to ROS formation at the BBB. Blocking ROS or Ca2+ signaling prevented H/R-induced monocyte adhesion to BEC. We conclude, that the activation of NMDAR under H/R by Glut increases intracellular Ca2+ levels, contributes to BBB disruption, ROS generation and monocyte adhesion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 449, Issue 3, 16 January 2009, Pages 168-172
Journal: Neuroscience Letters - Volume 449, Issue 3, 16 January 2009, Pages 168-172
نویسندگان
Christoph R.W. Kuhlmann, Christoph M. Zehendner, Marlis Gerigk, Dorothea Closhen, Bianca Bender, Peter Friedl, Heiko J. Luhmann,