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Updated: May 21, 2026
Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
MK-801 prevents overexpression of multidrug resistance protein 2 after status epilepticus
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.
Insights
N-methyl-D-aspartate (NMDA) receptor antagonists like MK-801 reduce multidrug resistance protein 2 (Mrp2) upregulation in the brain after seizures. This suggests NMDA receptors are key to Mrp2 changes at the blood-brain barrier during status epilepticus.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Status epilepticus (SE) can alter blood-brain barrier (BBB) function.
- Multidrug resistance protein 2 (Mrp2) is crucial for xenobiotic transport across the BBB.
- The role of N-methyl-D-aspartate (NMDA) receptors in regulating Mrp2 expression during SE is not fully understood.
Purpose of the Study:
- To investigate the involvement of NMDA receptors in the upregulation of Mrp2 expression following SE.
- To determine the impact of NMDA receptor blockade on Mrp2 levels and distribution in the brain.
Main Methods:
- Quantitative real-time polymerase chain reaction (qPCR) and Western blot were used to assess Mrp2 gene and protein expression at various time points post-SE.
- Immunofluorescence was employed to analyze the distribution of Mrp2 following administration of the NMDA receptor antagonist MK-801.
- Rats were subjected to SE, and Mrp2 expression was analyzed in hippocampal and other brain regions.
Main Results:
- SE induced a time-dependent upregulation of Mrp2 gene and protein in the hippocampus, peaking at 24 hours post-SE.
- Administration of MK-801 significantly prevented the SE-induced increase in Mrp2 expression.
- Immunofluorescence revealed that MK-801 attenuated the seizure-induced increase of Mrp2, particularly in brain capillaries, with significant upregulation observed in endothelial cells of the cerebral cortex, piriform cortex, and hippocampus.
Conclusions:
- NMDA receptors play a significant role in the upregulation of Mrp2 expression in the BBB following status epilepticus.
- Targeting NMDA receptors may offer a strategy to modulate Mrp2-mediated transport at the BBB during or after epileptic seizures.
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