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

Winfried Neuhaus (Corresponding author), Malgorzata Burek, Cholpon S. Djuzenova, Serge C. Thal, Hermann Koepsell, Norbert Roewer, Carola Förster

    Publications: Contribution to journalArticlePeer Reviewed

    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 6 h OGD, which was significantly reduced by 10 mu M 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.
    Original languageEnglish
    Pages (from-to)44-49
    Number of pages6
    JournalNeuroscience Letters
    Volume506
    Issue number1
    DOIs
    Publication statusPublished - 2012

    Austrian Fields of Science 2012

    • 301207 Pharmaceutical chemistry

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