The pilocarpine model of temporal lobe epilepsy

Understanding the pathophysiogenesis of temporal lobe epilepsy (TLE) largely rests on the use of modelsof status epilepticus (SE), as in the case of the pilocarpine model. The main features of TLE are: (i) epilepticfoci in the limbic system; (ii) an “initial precipitating injury”; (iii) the so-called “latent period”; and (iv)the presence of hippocampal sclerosis leading to reorganization of neuronal networks. Many of thesecharacteristics can be reproduced in rodents by systemic injection of pilocarpine; in this animal model, SEis followed by a latent period and later by the appearance of spontaneous recurrent seizures (SRSs). Theseprocesses are, however, influenced by experimental conditions such as rodent species, strain, gender, age,doses and routes of pilocarpine administration, as well as combinations with other drugs administeredbefore and/or after SE. In the attempt to limit these sources of variability,we evaluated themethodologicalprocedures used by several investigators in the pilocarpine model; in particular, we have focused on thebehavioural, electrophysiological and histopathological findings obtained with different protocols. Weaddressed the various experimental approaches published to date, by comparing mortality rates, onset ofSRSs, neuronal damage, and network reorganization. Based on the evidence reviewed here, we proposethat the pilocarpine model can be a valuable tool to investigate the mechanisms involved in TLE, and evenmore so when standardized to reduce mortality at the time of pilocarpine injection, differences in latentperiod duration, variability in the lesion extent, and SRS frequency.