title: Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells.
abstract: 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 6h OGD, which was significantly reduced by 10μM 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 6h OGD and was still higher (210%) after the 20h 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.
authors: Department of Anaesthesia and Critical Care, University of Wuerzburg, Oberdürrbacherstrasse 6, D-97080 Wuerzburg, Germany. winfried.neuhaus@univie.ac.at
authors: Winfried
authors: W
authors: Neuhaus
authors: Malgorzata
authors: M
authors: Burek
authors: Cholpon S
authors: CS
authors: Djuzenova
authors: Serge C
authors: SC
authors: Thal
authors: Hermann
authors: H
authors: Koepsell
authors: Norbert
authors: N
authors: Roewer
authors: Carola Y
authors: CY
authors: Förster
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D000860:Hypoxia / Q000188:drug therapy*; D051379:Mice; D010100:Oxygen / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014316:Tritium / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; D005947:Glucose; D010100:Oxygen