TY - JOUR
T1 - Farmacoresistenza e sclerosi ippocampale in un modello di epilessia del lobo temporale
T2 - Evidenze a favore di una relazione con la lesione dell'area CA3
AU - Longo, D.
AU - Baldelli, E.
AU - Manca, L.
AU - Gatti, G.
AU - Perucca, E.
AU - Avoli, M.
AU - Biagini, G.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Antiepileptic drug
KW - Hemorrhage
KW - Hippocampus
KW - Immunohistochemistry
KW - Ischemia
KW - Paradoxical effect
KW - Pharmacoresistance
KW - Pilocarpine
KW - Temporal lobe epilepsy
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M3 - Articolo
AN - SCOPUS:77953104045
SP - 113
EP - 116
JO - Bollettino - Lega Italiana contro l'Epilessia
JF - Bollettino - Lega Italiana contro l'Epilessia
SN - 0394-560X
IS - 138
ER -