The systemic administration of a potent muscarinic agonist pilocarpine in rats promotes sequential behavioral and electrographic changes that can be divided into 3 distinct periods: (a) an acute period that built up progressively into a limbic status epilepticus and that lasts 24 h, (b) a silent period with a progressive normalization of EEG and behavior which varies from 4 to 44 days, and (c) a chronic period with spontaneous recurrent seizures (SRSs). The main features of the SRSs observed during the long-term period resemble those of human complex partial seizures and recurs 2-3 times per week per animal. Therefore, the pilocarpine model of epilepsy is a valuable tool not only to study the pathogenesis of temporal lobe epilepsy in human condition, but also to evaluate potential antiepileptogenic drugs. This review concentrates on data from pilocarpine model of epilepsy.

Summary:Purpose: Animal models are useful for the study of status epilepticus (SE)-induced epileptogenesis and neurological sequelae, especially during early brain development. Here, we show several permanent abnormalities in animals subjected to multiple SE during early development.Methods: Wistar pup rats (7 to 9 days old) were subjected to three consecutive episodes of SE induced by systemic pilocarpine injections. To study the long-lasting consequences of early-induced SE, chronic electroencephalographic recordings were made from the hippocampus and cortex and several behavioral tests (inhibitory step-down avoidance, rota-rod, open field, elevated plus-maze, and Skinner box) were performed at postnatal days 30 to 90. We also investigated in vitro electrophysiological responses of the CA 1 area using extracellular recordings in hippocampal slices. A histological analysis was done using cresyl violet staining 24 hours and several months after SE induction. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL staining) 24 hours after the last SE episode.Results: Electroencephalographic recordings from 30-to 90-day-old rats that had been subjected to multiple SE episodes in early life showed marked changes compared with those from nontreated controls. These included frequent episodes of continuous complex spiking activity and high-voltage ictal discharges, with a small percentage of these rats presenting spontaneous behavioral seizures. These animals also presented evidence of severe cognitive deficit in adulthood. In vitro, a persistent hyperexcitability of the CAI area was detected in experimental animals. Histological analysis of the brains did not reveal any major long-term pathological changes. Nevertheless, an increased number of TUNEL-positive nuclei were present in some animals in both the hippocampus and the thalamus.Conclusions: These data show persistent abnormalities in animals subjected to multiple SE episodes during early postnatal development. SE may result in important plastic changes in critical periods of brain maturation leading to long-lasting epileptogenesis, as manifested by electrographic epileptiform discharges, behavioral deficits, and in vitro hyperexcitability of hippocampal networks.

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-The pilocarpine model of epilepsy in rats is characterised by the occurrence of spontaneous seizures (SRSs) during the chronic period that recur 2-3 times per week during the whole animal life. In a previous study on brain metabolism during the chronic period of the pilocarpine model it was possible to observe that, among several brain structures, the lateral posterior thalamic nuclei (LP) showed a strikingly increased metabolism. Some evidences suggest that the LP can participate in an inhibitory control system involved in the propagation of the seizures. The aim of the present study was to verify the role of LP in the expression and frequency of spontaneous seizures observed in the pilocarpine model. Ten adult male rats presenting SRSs were monitored for behavioural events by video system one month before and one month after LP ibotenic acid lesion. Another group of chronic epileptic rats (n=10) had the anteroventral thalamic nuclei (AV) lesioned by ibotenic acid. After the surgical procedure, the animals were sacrified and the brains were processed for histological analysis by the Nissl method. The LP group seizure frequency was 3.1±1.9 before ibotenic acid injection and showed an increase (16.3±7.2 per week) after LP lesion. No changes in SRSs frequency were observed in the AV group after ibotenic lesion in these nuclei. These results seem to suggest that LP play a role in the seizure circuitry inhibiting the expression of spontaneous seizures in the pilocarpine model. KEY WORDS: pilocarpine, lateral posterior thalamic nuclei.A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes A contribuição dos núcleos talâmico lateral posterior e anteroventral nas crises espontâneas e recorrentes no modelo de epilepsia induzido pela pilocarpina no modelo de epilepsia induzido pela pilocarpina no modelo de epilepsia induzido pela pilocarpina no modelo de epilepsia induzido pela pilocarpina no modelo de epilepsia induzido pela pilocarpina RESUMO -O modelo de epilepsia induzido pela pilocarpina é caracterizado pela ocorrência de crises espontâneas e recorrentes (CERs) durante o período crônico, em uma frequência de 2-3 episódios semanais durante toda a vida do animal. Um estudo prévio do metabolismo cerebral durante o período crônico do modelo da pilocarpina mostra que entre as diferentes estruturas cerebrais,o núcleo talâmico lateral posterior (LP) apresentou um significante aumento em seu metabolismo. Evidências sugerem que o LP pode participar como um sistema de controle inibitório na propagação das crises. O objetivo deste estudo foi verificar o papel do LP na expressão e frequência das CERs no modelo de epilepsia induzido pela pilocarpina. De...

Summary:Purpose: Interictal intervals in pilocarpineinduced chronic epilepsy are characterized by apparent normal electrographic activity and longer sleep periods or drowsiness or both. Sparse information exists concerning the neural network activity during these seizure-free intervals. In our research, a [ ''C]2-deoxy-~-glucose (2DG) autoradiographic technique was used to investigate interictal changes in the metabolism of the epileptic rat brain.Methods: Epileptic rats were monitored by video-EEG for -120 days, with [I4C]2DG injected after a seizure-free interval of 224 h.Results: Autoradiographic analysis revealed an increase in glucose utilization by several brain regions; the most consistent increase was found in the lateral posterior thalamic nucleus and pretectal region.Conclusions: These findings suggest that the lateral posterior thalamic nucleus and the pretectal region may be involved in cerebral circuits inhibiting epileptic activity during interictal intervals.

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