MODELS | Temporal Lobel Epilepsy in Humans: Searching for Answers through the Pilocarpine Model

Local or systemic administration of pilocarpine in rodents leads to a pattern of repetitive limbic seizures and status epilepticus (SE), which can last for several hours. A latent period follows SE and precedes a chronic phase, which is characterized by the occurrence of spontaneous limbic seizures. These distinct features, in a single animal preparation, of an acute damage induced by SE, a silent interval between injury and the onset of spontaneous seizures, and a chronic epileptic state have allowed investigators to develop antiepileptic drug (AED) studies with several purposes: (1) in the acute phase, identification of compounds with efficacy against refractory SE and/or neuroprotection against damage induced by sustained seizures; (2) in the latent period, identification of agents with a potential for preventing epileptogenesis and/or against seizure-induced long-term behavioral deficits; and (3) in the chronic phase, testing drugs effective against partial and secondarily generalized seizures. Studies using the pilocarpine model have suggested that some AEDs, as well as other (non-AED) compounds exert an antiepileptogenic effect. Drug testing in the chronic phase should address not only the suppression of secondarily generalized motor seizures, but also – using modern methods to quantify spontaneous electrical activity and sophisticated systems for assessing behavioral changes – partial seizure phenomena and associated disruption in cognitive and related behaviors.