Farmacoresistenza e sclerosi ippocampale in un modello di epilessia del lobo temporale: evidenze a favore di una relazione con la lesione dell’area CA3Pharmacoresistance and hippocampal sclerosis in a model of temporal lobe epilepsy: evidence for a relationship with lesion of the CA3 region

Temporal lobe epilepsy (TLE) with hippocampal sclerosis is the most common type of pharmacoresistantepilepsy in adults.We investigated whether hippocampal damage could influence the response to antiepilepticdrugs 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, weimplanted 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 animalsto assess the hippocampal damage.We found a highly predictable ischemic-hemorrhagic lesion in the CA3stratum lacunosum-molecolare of rats exposed to 120 min SE. Although ablating the perforant path terminalfield, this lesion was significantly (p < 0.05) less pronounced in animals with a SE of 30 minutes.All the rats wereresistant to CBZ.Moreover, rats exposed to 120 minutes of SE showed a 6-fold increase in frequency of spontaneousseizures during CBZ administration. These data suggest that the loss of direct inputs from the entorhinalcortex to CA3 can worsen the response to CBZ treatment in a model of TLE.