Fluvastatin prevents glutamate-induced blood-brain-barrier disruption in vitro

Kuhlmann, Christoph; Gerigk, Marlis; Bender, Bianca; Closhen, Dorothea; Leßmann, Volkmar; Luhmann, Heiko J.

doi:10.1016/j.lfs.2008.04.017

Cited by 47 publications

(39 citation statements)

References 34 publications

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“…A volume of 250 mmol/L glutamate did not affect TJ integrity (data not shown). Another key factor for BBB breakdown under pathologic conditions is the formation of ROS (Kuhlmann et al, 2008(Kuhlmann et al, , 2009b. To study the OGD-induced production of ROS in BEC within the coculture, the fluorescent ROS sensor 2 0 7 0 -dichlorodihydrofluorescein (DCF) (10 mmmol/L) was added 30 mins before picture acquisition.…”

Section: Immunohistochemistry Of Tight Junction Proteins Reactive Oxmentioning

confidence: 99%

Studying the Neurovascular Unit: An Improved Blood–Brain Barrier Model

Zehendner

Luhmann

Kuhlmann

2009

J Cereb Blood Flow Metab

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The blood-brain barrier (BBB) closely interacts with the neuronal parenchyma in vivo. To replicate this interdependence in vitro, we established a murine coculture model composed of brain endothelial cell (BEC) monolayers with cortical organotypic slice cultures. The morphology of cell types, expression of tight junctions, formation of reactive oxygen species, caspase-3 activity in BECs, and alterations of electrical resistance under physiologic and pathophysiological conditions were investigated. This new BBB model allows the application of techniques such as laser scanning confocal microscopy, immunohistochemistry, fluorescent live cell imaging, and electrical cell substrate impedance sensing in real time for studying the dynamics of BBB function under defined conditions.

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Section: Immunohistochemistry Of Tight Junction Proteins Reactive Oxmentioning

confidence: 99%

Studying the Neurovascular Unit: An Improved Blood–Brain Barrier Model

Zehendner

Luhmann

Kuhlmann

2009

J Cereb Blood Flow Metab

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“…ROS can cause mitochondrial damage [6]. In this context, it was recently reported that NMDAR inhibitor MK801 was able to block the upregulation of ROS formation and the following disruption of the barrier's integrity after hypoxia or glutamate stimuli in in vitro BBB models [11,12]. Thus, the first aim of the presented work was to investigate our hypothesis that MK801 can reduce the upregulation of glut1 during OGD in brain endothelial cells and to elucidate the contribution of this inhibition onto the total glucose uptake.…”

Section: Introductionmentioning

confidence: 99%

Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells

Neuhaus

Burek

Djuzenova

et al. 2012

Neuroscience Letters

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During stroke the blood-brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7-fold after six hours OGD, which was significantly reduced by 10 µM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after six hours OGD and was still higher (210%) after the 20 hours reoxygenation phase compared to normoxia. Ten µM MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.

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“…Its physiological content in the nervous tissue corresponds with the metabolic demand of the cells, and the BBB and BSCB protect CNS parenchyma from an influx of excessive extra-CNS glutamate amounts [26]. It is common knowledge that CNS glutamate concentration is greatly elevated in many CNS pathologies [23,35,43,48]. It has been demonstrated as well that the considerable ischemia-related elevation of intracerebral glutamate results in BBB damage and brain edema [41].…”

Section: Discussionmentioning

confidence: 99%