Antiepileptic drug-resistance is a major health problem in patients with
cortical dysplasia (CD). Whether
drug-resistant epilepsy is associated with progressive brain damage is still debated. We previously generated a rat model of acquired CD, the
methylazoxymethanol-
pilocarpine (MP) rat, in which the occurrence of
status epilepticus and subsequent spontaneous
seizures induce progressive brain damage (Nobili et al., 2015). The present study tested the outcome of early-chronic
carbamazepine (CBZ) administration on both seizure activity and brain damage in MP rats. We took advantage of the non-invasive CBZ-in-food administration protocol, established by Ali (2012), which proved effective in suppressing generalized convulsive
seizures in
kainic acid rat model of
epilepsy. MP rats were treated immediately after the onset of the first spontaneous seizure with 300 mg/kg/day CBZ formulated in pellets for a two-months-trial. CBZ-treated rats were continuously video-monitored to detect seizure activity and were compared with untreated epileptic MP rats. Despite CBZ serum levels in treated rats were within the suggested therapeutic range for humans, CBZ affected spontaneous convulsive
seizures in 2 out of 10 treated rats (responders), whereas the remaining animals (non-responders) did not show any difference when compared to untreated MP rats. Histological analysis revealed
cortical thinning paralleled by robust staining of Fluoro-Jade+ (FJ+) degenerating neurons and diffuse tissue
necrosis in CBZ-non-responder vs CBZ-responder rats. Data reported here suggest that MP rat model represents suitable experimental setting where to investigate mechanisms of CD-related
drug-resistant epilepsy and to verify if modulation of
seizures, with appropriate treatment, may reduce seizure-induced brain damage.