Farmacoresistenza e sclerosi ippocampale in un modello di epilessia del lobo temporale: Evidenze a favore di una relazione con la lesione dell'area CA3

Temporal lobe epilepsy (TLE) with hippocampal sclerosis is the most common type of pharmacoresistant epilepsy in adults.We investigated whether hippocampal damage could influence the response to antiepileptic drugs in the pilocarpine model of TLE. Sprague-Dawley rats were injected with intraperitoneal (i.p.) pilocarpine (380 mg/kg), and the provoked status epilepticus (SE) was quelled after 30 or 120 minutes with i.p. diazepam (20 mg/kg). After 3 weeks, when all the animals developed spontaneous recurrent seizures, we implanted osmotic minipumps to assure a constant release of carbamazepine (CBZ, 4 mg/kg/h) or vehicle (epileptic controls). After one week, during which we monitored seizure frequency, we sacrificed the animals to assess the hippocampal damage.We found a highly predictable ischemic-hemorrhagic lesion in the CA3 stratum lacunosum-molecolare of rats exposed to 120 min SE. Although ablating the perforant path terminal field, this lesion was significantly (p <0.05) less pronounced in animals with a SE of 30 minutes.All the rats were resistant to CBZ.Moreover, rats exposed to 120 minutes of SE showed a 6-fold increase in frequency of spontaneous seizures during CBZ administration. These data suggest that the loss of direct inputs from the entorhinal cortex to CA3 can worsen the response to CBZ treatment in a model of TLE.