We show that BI1029539, an mPGES-1 inhibitor, prevented up-regulation of P-gp expression and transport activity in capillaries exposed to glutamate and in capillaries from humanized mPGES-1 mice after SE.
Here, we report that a single 20-min status epilepticus (SE) induces P-gp and EPO-R expression in cortical pyramidal neurons and only P-gp expression in astrocytes.
In rats, repetitive seizures or status epilepticus induced high expression of P-gp and loss Kir expression in the brain and heart, and promoted membrane depolarization, malignant bradycardia, and the high rate of mortality.
We also demonstrated, <i>in vivo</i>, that cPLA2 inhibition prevents overexpression of P-gp and BCRP at the blood-brain barrier in rats after status epilepticus and in CE rats.
Perhaps, instead of stopping the subtherapeutic medication, the increasing doses of this AED and/or administration of inhibitors of CYP and P-glycoprotein, could help to achieve its therapeutic range, allowing a better pharmacologic effect and avoiding the development of more severe complications, such as status epilepticus or SUDEP.
FTY720 alleviated the overexpression of hippocampal P-gp in SE rats and reduced NF-κB activity and TNF-α and COX-2 expression, and W146 blocked the effects of FTY720.
Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy.
In the present study, Pgp expression was studied by immunohistochemistry in rats 24 h after a status epilepticus induced by either pilocarpine or kainate, widely used models of temporal lobe epilepsy.