Neurovascular Drug Biotransformation Machinery in Focal Human Epilepsies: Brain CYP3A4 Correlates with Seizure Frequency and Antiepileptic Drug Therapy.

ABSTRACT: Pharmacoresistance is a major clinical challenge for approximately 30% of patients with epilepsy. Previous studies indicate nuclear receptors (NRs), drug efflux transporters, and cytochrome P450 enzymes (CYPs) control drug passage across the blood-brain barrier (BBB) in drug-resistant epilepsy. Here, we (1) evaluate BBB changes, neurovascular nuclear receptors, and drug transporters in lesional/epileptic (EPI) and non-lesional/non-epileptic (NON-EPI) regions of the same brain, (2) examine regional CYP expression and activity, and (3) investigate the association among CYP brain expression, seizure frequency, duration of epilepsy, and antiepileptic drug (AED) combination. We used surgically resected brain specimens from patients with medically intractable epilepsy (n = 22) where the epilepto

SUBMITTER: Williams S 

PROVIDER: S-EPMC6854685 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature