Taking together, these data suggest that stimulation of EPO depending signaling system could not only play a central role in brain cell protection, but this system could be a new tool for reverse the pharmacoresistant phenotype in refractory epilepsy as well as in other pharmacoresistant hypoxic brain diseases expressing P-gp.
These data suggested that overexpression of P-gp and CYP3A during seizures and treated with CBZ may be regulated by PXR or NF-κB p65 activity and expression, which revealed a mechanism underlying the development of DRE.
Neuroinflammation due to high levels of glutamate has been identified as one of the causes of P-gp upregulation, and several studies in animal models of epilepsy suggest that antiinflammatory drugs might prevent P-gp overexpression and, thus, avoid the development of refractory epilepsy.
Consequently, RE and SUDEP share a multidrug resistance (MDR) phenotype, which is mainly associated with brain overexpression of ABC-transporters such as P-glycoprotein (P-gp).
We aimed to investigate the expression levels of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (P-gp) in peripheral blood of patients with refractory epilepsy.
The overexpression of multidrug transporters, as the P-glycoprotein (P-gp), at the level of the blood-brain barrier of epileptic patients has been suggested as a key mechanism underlying the refractory epilepsy.
Thus, our findings suggest that miR-298 reverses MDR to AEDs by inhibiting P-gp expression, suggesting a potential target for overcoming MDR in refractory epilepsy.
The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy.
The TT genotype of ABCB1rs717620 was also related with an increased risk of drug-resistant epilepsy (OR = 2.64, 95%CI = 1.03-7.13) compared to the CC+CT genotype in the recessive model.
The presented studies analysed the association between C3435T polymorphism of MDR1 gene and the incidence of drug-resistant epilepsy in the population of Polish children.
Previous studies have attempted to confirm the association between the ABCB1-C3435T polymorphism and drug-resistant epilepsy and produced discordant findings.
The obtained results clearly confirm the lack of a connection between the occurrence of drug-resistant epilepsy and C435T polymorphism of the MDR1 gene irrespective of the definition of drug resistance applied to the patient.
The relationship established in a subset of the Chinese population between the MDR1C3435T polymorphism and refractory epilepsy will guide epilepsy treatment and development of new AEDs.
To assess the association between MDR1C3435T polymorphism and the response to anticonvulsants in childhood intractable epilepsy, we conducted a systematic review and meta-analysis.