Spontaneous recurrent seizures and neuropathology in the chronic phase of the pilocarpine and picrotoxin model epilepsy

Abstract

In a recent publication, we have shown a potent interaction between the cholinergic and GABAergic systems in regard to seizure generation and developed the pilocarpine(pilo)/picrotoxin(PTX) model, in which combined injections of these agents have induced status epilepticus (SE) in rats. Here we report on the chronic features of this new animal model of epilepsy. Adult male Wistar rats were systemically injected with solutions containing 150/0.5 mg kg-1, 75/1.5 mg kg-1 and 50/2.0 mg kg-1 (pilo dose/PTX dose). Six epileptic and six control animals were observed for 120-131 days for the occurrence of spontaneous recurrent seizures (SRS). Electroencephalographic, neuropathologic and behavioral analyses were subsequently performed. Following SE, the animals went through a latent period and, subsequently, towards a state of 'chronic' epilepsy, characterized by the emergence of SRS. Animals that received 150/0.5 mg kg-1 presented a relatively short latent period, partial events as their most common initial seizure manifestations and a considerable subsequent progression towards generalization. The group injected with 75/1.5 mg kg-1 presented an extensive period during which the majority of the animals exclusively developed partial seizures (50 days). Animals injected with 50/2.0 mg kg-1 presented an average latent period of over 100 days. Only few animals within this group developed SRS. Our EEG, neuropathological and ictal behavioral findings, in conjunction with the fact that SE was required for the posterior development of SRS, suggest that our model parallels a human TLE condition. Even though diverse TLE models have been described, the pilo/PTX model has as a major feature the intriguing occurrence of disparities among these three groups in the chronic period, although no differences could be observed during SE induction. Future experiments conducted in this sense, might lead to important results in regard to the elucidation of mechanisms of epileptogenesis.