Summary:Purpose: The physiologic role of the cellular prion protein (PrP') is unknown. Mice devoid of PrPC develop normally and show only minor deficits. However, electrophysiologic and histologic alterations found in these mice suggest a possible role for PrP" in seizure threshold andor epilepsy.Methods: We tested the sensitivity of PrP" knockout mice to seizures induced by single convulsant or repeated subconvulsant (kindling) doses of pentylenetetrazol (PTZ), and to status epilepticus (SE) induced by kainic acid or pilocarpine.Results: In PTZ kindling, seizure severity progressed faster in the PrP' knockout group, in which 92.8% reached stage 5 or death after 4 days of stimulation, as opposed to 38.4% in wildtype animals. After 10 injections, mortality was 85.7% among knockouts and 15.3% among controls. After a single PTZ injection (60 mgkg), overall mortality due to seizures was 91 % in knockout mice, but only 33% among wild-type animals. Pilocarpine-induced SE (320 mgkg) caused an 86.7% mortality in knockouts, as opposed to 40% in wild-type animals. Finally, after kainic acid injections (10 mgkg), 70% of the knockouts developed at least one severe seizure, and 50% showed repetitive seizures, whereas no wild-type animal exhibited observable seizures.Conclusions: Animals lacking cellular prion protein expression are more susceptible to seizures induced by various convulsant agents. This is perhaps the most striking alteration yet found in PrP'-null mice, who at first analysis appeared to be completely normal. A possible role for PrP' in chronic and idiopathic (familial), secondary, or cryptogenic epilepsies in humans remains to be investigated. Key Words: PrionPrP"--Seizure-Epileps y-Kindling.Prions have long been known as the causative agents of spongiform encephalopathies, which can be transmitted through infection in livestock and humans but also by genetic inheritance in the latter (1). Their composition has been firmly established as consisting of a single protein termed scrapie prion protein (PrP'"). It has been shown that there are no differences between the amino acid sequences of PrP" and of its physiologic counterpart, cellular prion protein (PrP"). The only relevant difference between PrP"" and PrP" concerns their secondary structures, with the former displaying a much higher proportion of p-sheet conformational domains than the latter, which is mostly a-helical (2,3).The physiological function of PrP", however, remains unclear ( 1 4 ) . As it is located in the outer surface of cells, anchored by phosphatidylinositol glycolipid, it is a candidate for a signaling or, less likely, a transport function (3). Mice devoid of PrP" develop normally, showing normal learning (3,4), but have aberrant sleep patterns (3,5); moreover, one line of mice lacking PrP" developed cerebellar degeneration in old age (6). Mossy fiber alterations resembling those seen in temporal lobe epilepsy have recently been described in PrP" knockout mice (7). Moreover, one study has shown that y-aminobutyric acid type A (GABA,) rece...

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: Adenosine is a major negative neuromodulator of synaptic activity in the central nervous system and can exert anticonvulsant and neuroprotective effects in many experimental models of epilepsy. Extracellular adenosine can be formed by a membrane-anchored enzyme ecto-5 -nucleotidase. The purposes of this study were to characterize the role of adenosine receptors in modulating status epilepticus (SE) induced by pilocarpine and evaluate its neuroprotective action. Ecto-5 -nucleotidase activity was studied during the different phases of pilocarpine-induced epilepsy in rats.Methods: Adult rats were pretreated with different adenosinergic agents to evaluate the latency and incidence of SE induced by pilocarpine in rats. The neuroprotective effect also was evaluated.Results: A proconvulsant effect was observed with DPCPX and DMPX that reduced the latency of SE in almost all rats. Pretreatment with the MRS 1220 did not alter the incidence of SE but reduced the latency to develop SE. An anticonvulsant and neuroprotective effect was detected with R-PIA. Rats pretreated with R-PIA had a decreased number of apoptotic cells in the hippocampus, whereas pretreatment with DPCPX did not modify the hippocampal damage. An intensification of neuronal death was observed in the dentate gyrus and CA3 when rats were pretreated with DMPX. MRS-1220 did not modify the number of apoptotic cells in the hippocampus. An increase in the ecto-5´-nucleotidase staining was detected in the hippocampus during silent and chronic phases.Conclusions: The present data show that adenosine released during pilocarpine-induced SE via A1-receptor stimulation can exhibit neuroprotective and anticonvulsant roles. Similar effects could also be inferred with A2a and A3 adenosinergic agents, but further experiments are necessary to confirm their roles. Ecto-5´-nucleotidase activity during silent and chronic phases might have a role in blocking spontaneous seizures by production of inhibitory neuromodulator adenosine, besides taking part in the mechanism that controls sprouting.

The basal ganglia are involved in the organization of movement and function in the initiation and expression of generalized and limbic seizures. Dopamine is the principal neurotransmitter of the mesencephalic efferent pathways terminating in the mammalian striatum. No function has been ascribed to mesostriatal dopamine in the control of seizure spread in the brain. This work presents evidence that bilateral application of picomole amounts of apomorphine (a dopamine agonist) into the striatum confers protection against seizures produced by pilocarpine (a cholinergic agonist) in rats. The anticonvulsant effect of apomorphine is topographically confined to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Bilateral application of nanomolar amounts of haloperidol (a dopamine antagonist) into the caudate-putamen or systemic application of haloperidol both lower the threshold for pilocarpine-induced seizures. Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine. These results suggest that dopaminergic transmission in the striatum may be operative in complex neuronal networks modulating the seizure threshold.

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.

Summary:Purpose: Clinical, neuropathological, and electrophysiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). In most cases, limbic-originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. The present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine-treated epileptic rats.Methods: Adult epileptic animals showing six to seven seizures/week and saline-injected rats were selected for neurohistology. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and stained with cresyl violet (Nissl). Immunocytochemistry (ICC) was performed using anti-neurofilament (SMI-311) antibody. Extracellular (layer II/III) and intracellular (layer V) recordings were performed in coronal sensorimotor neocortical slices. Several electrophysiological aspects were examined such as evoked responses, intrinsic properties, and firing patterns of layer V pyramidal cells.Results: Nissl staining showed a significant decrease of cortical thickness in epileptic rats when compared with controls, particularly in superficial layers (II-IV). Such abnormalities were also revealed by SMI-311 staining. SMI-311-labeled dendrite arborizations were more complex in layers I-II of epileptic rats. Epileptic rats manifested several abnormalities in extracellular field responses including hyperresponsiveness and presence of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-mediated polysynaptic activity. Although no significant changes were observed concerning passive intrinsic properties, it was possible to detect a higher proportion of bursting neurons distributed in layer V (60%) of epileptic rats compared with 22% in control slices.Conclusions: Taken together, our findings indicate damage, reorganization, and chronic hyperexcitability of sensorimotor neocortex in experimental TLE.

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People with epilepsy suffer from a considerable lack of physical activity. In addition, an important problem of epilepsy management is the lack of qualified professionals. In this study we present data from a survey which aimed to assess physical educators' general knowledge about epilepsy. One hundred and thirty four physical educators of both sexes answered a questionnaire. Sixty percent of the professionals believe that a seizure is an abnormal electrical discharge of the brain, 13% that epilepsy is a cerebral chronic disease that can not be cured or controlled, 84% that people having convulsions will not necessarily present epilepsy and 5% that people with epilepsy have difficulties of learning. Questions concerned previous professional experience with epilepsy showed that 61% have seen a seizure and 53% have access to some information about epilepsy. Thus, 28% of professionals have a friend or relative with epilepsy, 14% have a student with epilepsy, and 29% helped someone during seizures. Our findings reveal a lack of physical educators' appropriate knowledge about epilepsy. Improvement of this might contribute to the improvement of epilepsy care/management. Key words: physical activity, physical education, epilepsy, knowledge.Avaliação do conhecimento de professores de educação física sobre epilepsia RESUMO Pessoas com epilepsia apresentam baixa participação em atividades físicas. Um importante problema nos cuidados da epilepsia é a falta de profissionais qualificados. Neste estudo apresentamos dados de uma pesquisa para avaliar o conhecimento de professores de educação física sobre a epilepsia. Um questionário foi respondido por 134 educadores físicos de ambos os sexos. Sessenta por cento dos profissionais acreditam que a crise epilética é uma descarga elétrica anormal do cérebro, 13% que a epilepsia é uma doença crônica cerebral que não pode ser curada ou controlada, 84% que pessoas que têm convulsões não necessariamente apresentam epilepsia e 5% que pessoas com epilepsia têm dificuldade de aprendizado. Em relação à experiência prévia do profissional, 61% presenciaram uma crise epilética e 53% tiveram acesso a alguma informação sobre epilepsia. Além disso, 28% dos profissionais possuíam amigo ou parente com epilepsia, 14% tinham um aluno com epilepsia e 29% já tinham socorrido alguém durante uma crise. Nossos achados revelam uma falta de conhecimento apropriado dos profissionais da área de educação física sobre a epilepsia. A melhora desse conhecimento pode contribuir para um adequado tratamento e cuidado da pessoa com epilepsia.