Recent arouse of interest indicated that
drug resistant
proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these
drug resistant
proteins, the enhanced function of such
proteins may increase
drug extrusion, resulting in inadequate response to
drug therapy in patients with
epilepsy. We studied expression of the
multidrug resistance protein 1 (MDR1) and
multidrug resistance-associated protein 1 (
MRP1) in the epileptic tissues resected surgically in 28 patients with
focal cortical dysplasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while
MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and
MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong
MRP1 immunoreactivity. Endothelial cells showed both MDR1 and
MRP1 expression in the majority of the specimens studied. Multidrug transporters are over-expressed in the epileptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug
proteins were shown in epileptogenic brain tissue in patients with FCD, that the over-expression of
drug transport proteins in tissue from patients with
refractory epilepsy may explain one possible mechanism for
drug resistant in these pathologies.