Neuroethological study of status epilepticus induced by systemic pilocarpine in Wistar audiogenic rats (WAR strain).

The administration of pilocarpine (PILO) is widely recognized as resulting in an experimental model of temporal lobe epilepsy; it is characterized by induction of status epilepticus (SE) and spontaneous recurrent seizures after a latent period. We provide in this work a neuroethological description of the SE induced by PILO. Behavioral evaluations were made in Wistar Audiogenic Rats (WARs) and Wistar resistant (R) animals. The experimental group (R) and WARs were pretreated with methyl scopolamine (1mg/kg ip) and injected with PILO (R animals, 340-380 mg/kg ip; WARs, 240-280 mg/kg ip). Among R animals, 36% developed SE, and among WARs, 53%. The control group (R animals and WARs) was injected only with methyl scopolamine plus saline. The ETHOMATIC method was used for evaluation of seizures. Sequences included in the analysis were chosen using (1) fixed observation windows and (2) behavioral triggers. The R group showed that the threshold for seizure is variable, so seizure onset and behavioral evolution were better described using behavioral triggers than fixed observation windows. The observation windows selected in similar duration intervals do not characterize the seizures. Sequential analysis in the WAR group showed high mortality after SE and greater susceptibility to PILO, compared with R animals. We conclude that with neuroethological tools it is possible to better map the sequence and evolution of SE induced by PILO compared to only using behavioral and arbitrary seizure severity scales. This sequence is faster and stronger in severity when WARs are compared with R animals. Although the WARs underwent an evolution of SE in some way equivalent to that of R animals, some rats presented tonic-clonic convulsions after PILO injection, very similar to acute audiogenic seizures, a brainstem-dependent model. The current data also point to the PILO-plus-WAR combination as a suitable protocol to study the genetic-epilepsy connection in experimental temporal lobe epilepsy.

Behavioral, morphologic, and electroencephalographic evaluation of seizures induced by intrahippocampal microinjection of pilocarpine.

PURPOSE: We studied, by means of video-EEG and neo-Timm histochemistry, the behavioral, electrophysiologic, and structural characteristics of seizures induced by intrahippocampal microinjection of pilocarpine (HIP-PILO), a selective model of temporal lobe epilepsy (TLE). METHODS: We investigated the behavioral and electrophysiologic (hippocampus and amygdala EEG) evaluation of status epilepticus (SE) induced by HIP-PILO and the consequent spontaneous recurrent seizures (SRSs). We evaluated hippocampal structural rearrangements after SE by means of neo-Timm staining. RESULTS: HIP-PILO induced SE in 17 (71%) of 24 animals. Although three animals displayed spontaneous remission of SE (not used in analysis) before the established SE duration (90 min), none of those undergoing SE died. Of SE animals, 10 (71%) of 14 had SRSs. All animals with SE had clear-cut mossy fiber sprouting (MFS) in the inner molecular layer of the dentate gyrus and epileptiform activity in hippocampus and amygdala. CONCLUSIONS: HIP-PILO rats displayed SE, SRS, MFS, and limbic epileptiform activity, without animal loss after SE. Thus, our data support this as a selective and efficient model of TLE.