The lesional and epileptogenic consequences of lithium-pilocarpine-inducedstatus epilepticus are affected by previous exposure to isolated seizures:Effects of amygdala kindling and maximal electroshocks

In temporal to be epilepsy, the occurrence of seizures seems to correlate w ith the presence of lesions underlying the establishment of a hyperexcitabl e circuit. However, in the lithium-pilocarpine model of epilepsy, neuronal damage occurs both in the structures belonging to the circuit of initiation and maintenance of the seizures (forebrain limbic system) as in the propag ation areas (cortex and thalamus) and in the circuit of remote control of s eizures (substantia nigra pars reticulata). To determine whether or not we could protect the brain from lesions and epileptogenesis induced by status epilepticus and identify cerebral structures involved in the genesis of epi lepsy, eve studied the effects of the chronic exposure to non-deleterious s eizures, either focalized with secondary generalization (amygdala kindling, kindled-pilocarpine rats), or primary generalized (ear-clip electroshocks, electroshock-pilocarpine rats) on neuronal damage and epileptogenesis indu ced by lithium-pilocarpine status epilepticus. These animals were compared to rats subjected to status epilepticus but not pretreated with seizures (s ham-kindled-pilocarpine or sham-electro-shock-pilocarpine rats). Compared t o sham-pilocarpine rats, neuronal damage was prevented in the limbic system of the kindled-pilocarpine rats, except in the hilus of the dentate gyrus and the entorhinal cortex, while it was enhanced in rats pretreated with el ectroshocks, mainly in the entorhinal and perirhinal cortices. Mostsham-kin dled- and sham-electroshocli-pilocarpine fats (92-100%) developed recurrent seizures after a silent period of 30-54 days. Likewise, all kindled-piloca rpine rats developed spontaneous seizures after the same latency as their s ham controls, while only two of 10 electroshock-pilocarpine rats became epi leptic after a delay of 106-151 days. The present data show that the apparent antiepileptic properties of electro shocks correlate with extensive damage in midbrain cortical regions, which may prevent the propagation of seizures from the hippocampus and inhibit th eir motor expression. Conversely, the extensive neuroprotection of the limb ic system but not the hilus and entorhinal cortex provided by amygdala kind ling does not prevent epileptogenesis. Thus, the hilus, the entorhinal and/ or perirhinal cortex may be key structure(s) for the establishment of epile psy. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.