5459
2012
eng
article
1
2012-01-30
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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
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.
urn:nbn:de:bvb:20-opus-67241
6724
Neuroscience Letters (2012) 506, 44– 49; http://dx.doi.org/10.1016/j.neulet.2011.10.045
241778
Deutsches Urheberrecht
Winfried Neuhaus
Malgorzata Burek
Cholpon C Djuzenova
Serge C Thal
Hermann Koepsell
Norbert Roewer
Carola Y Förster
deu
swd
Blut-Hirn-Schranke
deu
swd
Schlaganfall
deu
swd
Glucosetransportproteine
deu
swd
NMDA-Antagonist
deu
swd
NMDA-Rezeptor
eng
uncontrolled
blood-brain barrier
eng
uncontrolled
MK801
eng
uncontrolled
NMDAR
eng
uncontrolled
stroke
eng
uncontrolled
glut1
eng
uncontrolled
sglt1
Medizin und Gesundheit
open_access
Institut für Anatomie und Zellbiologie
Klinik und Poliklinik für Anästhesiologie (ab 2004)
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5459/Foerster_Neuhaus_NeuroscienceLetters506.pdf
17098
2017
eng
894-906
4
8
article
1
2018-11-02
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Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm\(^{2}\) and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.
Stem Cell Reports
10.1016/j.stemcr.2017.02.021
28344002
urn:nbn:de:bvb:20-opus-170982
Stem Cell Reports 2017, 8(4), 894-906. DOI: 10.1016/j.stemcr.2017.02.021
false
true
CC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International
Antje Appelt-Menzel
Alevtina Cubukova
Katharina Günther
Frank Edenhofer
Jörg Piontek
Gerd Krause
Tanja Stüber
Heike Walles
Winfried Neuhaus
Marco Metzger
eng
uncontrolled
blood-brain barrier (BBB) model
eng
uncontrolled
human induced pluripotent stem cells (hiPSCs)human induced pluripotent stem cells (hiPSCs)
eng
uncontrolled
multipotent fetal neural stem cells (fNSCs)
eng
uncontrolled
neurovascular unit in vitro
Medizin und Gesundheit
open_access
Frauenklinik und Poliklinik
Institut für Anatomie und Zellbiologie
Lehrstuhl für Tissue Engineering und Regenerative Medizin
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17098/082_Appelt-Menzelt_STEM-CELL-RESEARCH.pdf