Over-expression of P-glycoprotein in the canine brain following spontaneous status epilepticus

Therefore, we immunohistologically studied expression of the major BBB efflux transporter P-glycoprotein (Pgp) in brain tissue sampled from epileptic dogs following spontaneous seizure clusters or status epilepticus. Data were compared with tissue from control dogs that were euthanized due to non-CNS diseases. Following a status epilepticus, a significant up-regulation of endothelial Pgp expression by 87-166% was revealed in the hilus and the granule cell layer of the dentate gyrus as well as in the parietal cortex. In view of the suggested role of Pgp in drug-refractoriness its up-regulation in response to spontaneous prolonged seizure activity may be of specific relevance for subsequent therapeutic outcome. Moreover, our findings indicate that molecular changes in dogs with refractory epilepsy reflect those in human epileptic patients, thereby suggesting epileptic dogs as a suitable model of pharmacoresistant epilepsy. Clinical studies with Pgp modulating compounds are currently envisaged in canine epilepsy.