ArticleEpilepsia2018
Modulation of glucocorticoid receptor in human epileptic endothelial cells impacts drug biotransformation in an in vitro blood-brain barrier model.
Article in Epilepsia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Liver-nervous system axis: pathways, dysregulation, and translational perspectives.Journal of neuroinflammation · 2026Review
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- The role of molecular chaperones in the mechanisms of epileptogenesis.Cell stress & chaperones · 2023Review
- Glucocorticoid Receptor β Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication.International journal of molecular sciences · 2022Article
- Cortical Dysplasia in Rats Provokes Neurovascular Alterations, GLUT1 Dysfunction, and Metabolic Disturbances That Are Sustained Post-Seizure Induction.Molecular neurobiology · 2022Article
- Intestinal Flora Composition Determines Microglia Activation and Improves Epileptic Episode Progress.Frontiers in cellular and infection microbiology · 2022Article
- Cytochrome P450-mediated antiseizure medication interactions influence apoptosis, modulate the brain BAX/Bcl-XFrontiers in pharmacology · 2022Article
- Drug Delivery Challenges in Brain Disorders across the Blood-Brain Barrier: Novel Methods and Future Considerations for Improved Therapy.Biomedicines · 2021Review
- Multiple hurdle mechanism and blood-brain barrier in epilepsy: glucocorticoid receptor-heat shock proteins on drug regulation.Neural regeneration research · 2021Review
- Heat Shock Proteins Accelerate the Maturation of Brain Endothelial Cell Glucocorticoid Receptor in Focal Human Drug-Resistant Epilepsy.Molecular neurobiology · 2020Article
- In vitro modeling of blood-brain barrier and interface functions in neuroimmune communication.Fluids and barriers of the CNS · 2020Review
- Review
- Neurovascular glucocorticoid receptors and glucocorticoids: implications in health, neurological disorders and drug therapy.Drug discovery today · 2020Review
- Neurovascular Drug Biotransformation Machinery in Focal Human Epilepsies: Brain CYP3A4 Correlates with Seizure Frequency and Antiepileptic Drug Therapy.Molecular neurobiology · 2019Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveNuclear receptors and cytochrome P450 (CYP) regulate hepatic metabolism of several drugs. Nuclear receptors are expressed at the neurovascular unit of patients with drug-resistant epilepsy. We studied whether glucocorticoid receptor (GR) silencing or inhibition in human epileptic brain endothelial cells (EPI-ECs) functionally impacts drug bioavailability across an in vitro model of the blood-brain barrier (BBB) by CYP-multidrug transporter (multidrug resistance protein 1, MDR1) mechanisms.
methodsSurgically resected brain specimens from patients with drug-resistant epilepsy, primary EPI-ECs, and control human brain microvascular endothelial cells (HBMECs) were used. Expression of GR, pregnane X receptor, CYP3A4, and MDR1 was analyzed pre- and post-GR silencing in EPI-ECs. Endothelial cells were co-cultured with astrocytes and seeded in an in vitro flow-based BBB model (DIV-BBB). Alternatively, the GR inhibitor mifepristone was added to the EPI-EC DIV-BBB. Integrity of the BBB was monitored by measuring transendothelial electrical resistance. Cell viability was assessed by glucose-lactate levels. Permeability of [
resultsSilencing and inhibition of GR in EPI-ECs resulted in decreased pregnane X receptor, CYP3A4, and MDR1 expression. GR silencing or inhibition did not affect BBB properties in vitro, as transendothelial electrical resistance and P SIGNIFICANCE: Our results suggest that modulating GR expression in EPI-ECs at the BBB modifies drug metabolism and penetration by a mechanism encompassing P450 and efflux transporters. The latter could be exploited for future drug design and to overcome pharmacoresistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.