Spontaneous seizures preferentially injure interneurons in the pilocarpine model of chronic spontaneous seizures

It is still a question of much debate whether single epileptic seizures can cause cell loss. Despite the clinical impression that epilepsy in generalis a progressive disorder, experimental evidence is not conclusive on this point. Recently, it has been shown that electrically-induced afterdischarges of less than 2 min may induce structural impairments in neurons. Here we evaluated whether spontaneous seizures would lead to similar impairments. Chronic spontaneous recurrent seizures were induced with pilocarpine (320 mg/kg, i.p.). Animals were sacrificed from 1 to 6 h either after single or multiple seizures. A Golgi-like sensitive silver-impregnation procedure was used to reveal injured neurons. Silver-impregnated dark neurons were never found in control animals nor in epileptic animals that had no behavioral seizures in the 8 h prior to sacrifice. After spontaneous seizures (injured) dark neurons were mostly interneurons and were present in hippocampus (CA1 stratum radiatum), amygdala, piriform cortex and other limbic structures. Animals with multiple seizures had a higher number of dark cells than animals with single seizures. Our findings suggest that even single generalized spontaneous tonic-clonic seizures can induce long-lasting morphological changes. Our results favor the idea that epilepsy is a progressive disorder where one seizure begets the next.