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  • Title: MK-801 prevents overexpression of multidrug resistance protein 2 after status epilepticus.
    Author: Hao Y, Wu X, Xu L, Guan Y, Hong Z.
    Journal: Neurol Res; 2012 Jun; 34(5):430-8. PubMed ID: 22643638.
    Abstract:
    OBJECTIVE: The aim of this study was to investigate whether NMDA receptor was involved in the upregulation of multidrug resistance protein 2 (Mrp2) expression during status epilepticus (SE). METHODS: The alterations in the expression of Mrp2 at various time points after SE, and the inhibition of glutamate N-methyl-D-aspartate (NMDA) receptor on Mrp2 expression in hippocampus were both tested by quantitative real-time polymerase chain reaction and western blot. Moreover, immunofluorescence was also used to analyze the impact of the NMDA receptor antagonist, MK-801, on the distribution of Mrp2 in different brain areas. RESULTS: The results showed that gene encoding Mrp2 was upregulated in hippocampus at 6 hours after the end of SE, and this initial increase was followed by gradual normalization. While between 3 and 72 hours after the end of SE, the protein level of Mrp2 was upregulated in hippocampus, with the highest level emerging at 24 hours. The increment of Mrp2 gene and protein induced by SE was prevented by MK-801 at 6 and 24 hours respectively after the end of SE in the hippocampus. Moreover, immunofluorescence showed that seizures-induced increase of Mrp2 expression was attenuated by the administration of MK-801 mainly in capillaries. Rats after SE exhibited a significant upregulation of Mrp2 in the capillary endothelial cells of the cerebral cortex, piriform cortex, and hippocampus, compared with those in control at 24 hours after the end of SE. CONCLUSION: The results indicated that the NMDA receptor plays an important role in the upregulation of Mrp2 expression in the blood-brain barrier.
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