| Background One-third of patients with epilepsy suffer from intractable seizures, which cannot be properly controlled with the current pharmacotherapy.Most patients with temporal lobe epilepy(TLE), show a unique type of hippocampal damage, referred to as hippocampal sclerosis, which is characterized by extensive cell loss in the CA3 and CA1 sectors and the hilus of the dentate gyrus A variety of experimental and clinical observations suggests that this hippocampal damage can be both the result of seizure activity and the cause of further chronic epilepsy .Possible explanations for this phenomenon are: (1) targets for antiepileptic drugs (AEDs) are lost or altered (e.g. sodium channels or GAB A receptors), and/or (2) inappropriate penetration of AEDs into the brain, due to alterations in drug transporters at the blood-brain barrier (BBB). Drug efflux transporters such as P-glycoprotein (P-gp) might be important in this respect.In recently years, .some sdudies show that expression of the multidrug resistance gene(mdr1a and mdr1b) and p-glycoprotein encoded by mdr1a and mdr1b are high in the brain,especially in the hippocampus,and the expression may lead to reduce AEDs concentration in the brain.But these studies are most focus on acute epileptic activity shortly after status epilepticus (SE), spontaneous seizures are seldom studied.We used a rat model of kainic acid induced spontaneous seizures.Objective.We investigated express of mdr1a and mdr1b mRNA, and explore whether topiramate(TPM) affect express of mdr1a and mdr1b in the hippocampus of spontaneous seizures rat.Methods Seizures were induced by intraperitoneal injection of 10 mg/kg kainic acid at postnatal day 28. control rats were injected with sodium chloride.All rats were... |
