TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Burek, Malgorzata
A1  - Djuzenova, Cholpon C
A1  - Thal, Serge C
A1  - Koepsell, Hermann
A1  - Roewer, Norbert
A1  - Förster, Carola Y
T1  - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells
N2  - 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 6 h 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 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar 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.
KW  - Blut-Hirn-Schranke
KW  - Schlaganfall
KW  - Glucosetransportproteine
KW  - NMDA-Antagonist
KW  - NMDA-Rezeptor
KW  - blood-brain barrier
KW  - MK801
KW  - NMDAR
KW  - stroke
KW  - glut1
KW  - sglt1
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67241
ER  - 
TY  - JOUR
A1  - Salvador, Ellaine
A1  - Burek, Malgorzata
A1  - Förster, Carola Y.
T1  - Stretch and/or oxygen glucose deprivation (OGD) in an in vitro traumatic brain injury (TBI) model induces calcium alteration and inflammatory cascade
JF  - Frontiers in Cellular Neuroscience
N2  - The blood-brain barrier (BBB), made up of endothelial cells of capillaries in the brain, maintains the microenvironment of the central nervous system. During ischemia and traumatic brain injury (TBI), cellular disruption leading to mechanical insult results to the BBB being compromised. Oxygen glucose deprivation (OGD) is the most commonly used in vitro model for ischemia. On the other hand, stretch injury is currently being used to model TBI in vitro. In this paper, the two methods are used alone or in combination, to assess their effects on cerebrovascular endothelial cells cEND in the presence or absence of astrocytic factors. Applying severe stretch and/or OGD to cEND cells in our experiments resulted to cell swelling and distortion. Damage to the cells induced release of lactate dehydrogenase enzyme (LDH) and nitric oxide (NO) into the cell culture medium. In addition, mRNA expression of inflammatory markers interleukin (I L)-6, IL-1\(\alpha\) chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor (TNF)-\(\alpha\) also increased. These events could lead to the opening of calcium ion channels resulting to excitotoxicity. This could be demonstrated by increased calcium level in OGD-subjected cEND cells incubated with astrocyte-conditioned medium. Furthermore, reduction of cell membrane integrity decreased tight junction proteins claudin-5 and occludin expression. In addition, permeability of the endothelial cell monolayer increased. Also, since cell damage requires an increased uptake of glucose, expression of glucose transporter glut1 was found to increase at the mRNA level after OGD. Overall, the effects of OGD on cEND cells appear to be more prominent than that of stretch with regards to TJ proteins, NO, glutl expression, and calcium level. Astrocytes potentiate these effects on calcium level in cEND cells. Combining both methods to model TBI in vitro shows a promising improvement to currently available models.
KW  - receptor antagonist
KW  - cytokine expression
KW  - tight junctions
KW  - cell stretch
KW  - calcium level
KW  - nitric oxide
KW  - endothelial cells
KW  - necrosis factor alpha
KW  - barrier properties
KW  - cerebral ischemia
KW  - nervous system
KW  - CNS injury
KW  - blood brain barrier
KW  - cEND
KW  - astrocytes
KW  - traumatic brain injury
KW  - oxygen-glucose deprivation
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148255
VL  - 9
IS  - 323
ER  -