La sclérose tubéreuse de Bourneville (STB) est une maladie génétique et multi-systémique à transmission autosomique dominante due à des mutations d’un gène TSC1 ou TSC2 qui codent respectivement pour hamartine et tuberine ayant une action inhibitrice sur la voie de signalisation mTOR. L’épilepsie précoce et pharmacorésistante est la manifestation neurologique la plus fréquente et la plus délétère de la STB. Elle débute souvent dans la première année de vie par des spasmes infantiles qui évoluent avec l’âge et en absence de traitement vers des crises toniques ou tonico-cloniques. Bien que les crises soient supposées être générées dans des tubers corticaux, les mécanismes de l’épilepsie ne sont pas bien élucidés et le traitement reste souvent inefficace. Des études morphologiques ont montré une altération de l’expression ARNm des récepteurs au glutamate dans les cellules géantes et les neurones dysplasiques des tubers, mais leur implication fonctionnelle restait à montrer. Les différentes sous-unités NMDA ont une expression âge-dépendante et région-spécifique, les plus grands changements survenant au début de la vie quand l’épilepsie de la STB apparaît. Ce travail avait pour but d’étudier à l’aide de méthodes électrophysiologiques in vitro et in vivo l’expression fonctionnelle des sous-unités NMDA aberrantes et de déterminer leur rôle dans l’épileptogènese chez les souris hétérozygotes Tsc1+/- et sur le tissu humain STB post-opératoire. Nous avons pu démontrer que : i) Les souris hétérozygotes pour le gène Tsc1 sont spontanément épileptiques in vivo et in vitro dans une courte fenêtre dévelopmentale de P9 à P18. ii) Elles présentent une altération d’expression des récepteurs NMDA couche-spécifique et mTOR dépendante avec une surexpression des sous-unités GluN2C/D dans la couche 4 et 2/3 et GluN2B dans les couches 2/3. Cette expression anormale est prévenue par l’administration d’un inhibiteur de la voie mTOR, la rapamycine. iii) Les mêmes altérations d’expression des récepteurs NMDA, sont montrées sur les tissus post-opératoires, non seulement de tubers de STB mais aussi des dysplasies corticales focales (DCF), ces deux malformations ayant des similarités étiologiques et physiopathologiques. iv) La RT-PCR quantitative confirme une expression excessive de GluN2C dans le cortex de souris Tsc1+/- et sur le tissu humain des tubers et DCF. v) Les décharges épileptiques chez la souris Tsc1+/- sont générées dans la couche granulaire 4 du cortex avant de se propager vers les couches superficielles et les couches profondes, empruntant ainsi les microcircuits corticaux. vi) L’expression excessive de la sous-unité GluN2C dans le cortex contribue à l’hyperexcitabilité neuronale chez la souris Tsc1+/- et sur des tissus humains de tubers et de DCF puisque les crises et les décharges sont bloquées par les antagonistes sélectifs de GluN2C/D. vii) Les crises chez la souris Tsc1+/- suivent une séquence âge-dépendante évoluant du type «spasms-like» vers «tonic-clonic like», rappelant celle de l’épilepsie humaine, avec deux pics de haute incidence de crises à P13 et P16 correspondant chez l’homme respectivement l’âge des spasmes infantiles et celui des crises toniques. L’évolution avec l’âge du délai de propagation inter-hémisphérique pourrait contribuer à ce changement de types de crises. Ces résultats montrent donc pour la première fois qu’une happloinsuffisance pour le gène Tsc1 chez les souris Tsc1+/- sans tubers suffit à produire une altération de l’expression des récepteurs NMDA de manière mTOR dépendante et contribuer ainsi à l’épileptogènese dans la STB. La souris Tsc1+/- est le premier modèle génétique sans anomalies morphologiques présentant une épilepsie spontanée qui évolue des spasmes vers des crises toniques et tonico-cloniques. Néanmoins cette épilepsie diffère de l’épilepsie humaine de la STB par l’absence de crises focales et de pharmacorésistance, ce qui pourrait être expliqué par l’absence de tubers chez la souris Tsc1+/-. (...) / Tuberous sclerosis complex (TSC) is a genetic multisystemic disease with autosomal dominant transmission due to mutations in a gene TSC1 or TSC2 respectively which encode hamartin and tuberin proteins having an inhibitory action on the mTOR signaling pathway. Early refractory epilepsy is the most common and most deleterious neurological manifestation. The epilepsy often begins in the first year of life by infantile spasms that change in the lack of treatment to tonic or tonic-clonic seizures in age-dependent manner. Although seizures are thought to be generated in cortical tubers, epilepsy mechanisms are not well understood and treatment is often ineffective. Morphological studies showed the altered expression of glutamate receptor mRNA in the giant cells and dysplastic neurons of tubers, but their functional involvement remains unknown. The different NMDA subunits have an age-dependent and region-specific expression, the greatest changes occurring early in life when the TSC epilepsy appears. This work aimed to study the functional expression of aberrant NMDA subunits expression and their role in the epileptogenesis in heterozygous Tsc1+/- mice and post-surgical human tissue of TSC patients using in vitro and in vivo electrophysiological methods. The study reveal that: i) Heterozygous tuber-free Tsc1+/- mice show spontaneous epilepsy in vivo and in vitro in a short developmental window from P9 to P18. ii) These mice exhibit an altered NMDA receptor expression in mTOR dependent and layer-specific manner with GluN2C/D subunits overexpression in layers 4 and 2/3, and GluN2B ovexpression in layers 2/3. This abnormal NMDA receptors expression is prevented by the administration of an mTOR inhibitor, rapamycin. iii) The same alterations of NMDA receptors’ expression are shown in post-surgical tissues not only in tubers from TSC patients, but also in focal cortical dysplasia (FCD), these two malformations sharing etiological and pathophysiological similarities. iv) Quantitative RT-PCR confirms the excessive GluN2C subunit expression in Tsc1+/- mouse cortex and human tissue of tubers and DCF. v) Epileptic discharges in Tsc1+/- mice are generated in the granular layer 4 of the cortex before spreading to the superficial and then to deep layers, thus borrowing the cortical microcircuits. vi) Excessive expression of GluN2C subunit in the cortex contributes to neuronal hyperexcitability in Tsc1+/- mice, as well as in human tubers and DCF tissues, since epileptic discharges are blocked by selective GluN2C/D antagonists. vii) Seizures in Tsc1+/- mice follow the age-dependent sequence, evolving from "spasms-like" to "tonic-clonic like" thus reminding the human epilepsy, with two peaks of highest seizure incidence at P13 and P16 corresponding respectively to age of infantile spasms and of tonic seizures in human. The age-dependent evolution of interhemispheric propagation delay could contribute to this change in seizure type. These results show for the first time that TSC1 happloinsuffisancy in tuber-free Tsc1+/- mice is sufficient to produce an alteration in NMDA receptor expression in an mTOR dependent manner, and thus contributes to epileptogenesis in TSC. The Tsc1+/- mouse line is the first genetic model of TSC without morphological abnormalities presenting with early spontaneous seizures which evolves from “spasms-like” to “tonic-clonic like” seizures. However, the epilepsy in Tsc1+/- mice differs from human TSC epilepsy by the absence of focal seizures and of drug-resistance. Both could be explained by the lack of tubers in the Tsc1+/- mice. It remains to determine whether the expression of GluN2C subunit is also transitional in Tsc1+/- mice and whether other factors contribute to determine the age-dependent epilepsy. This study opens new therapeutic perspectives of TSC epilepsy targeting GluN2C subunit of NMDA receptors.

Transitions between normal and pathological brain states are manifested differently in the electroencephalogram (EEG). Traditional discrimination of these states is often subject to bias and strict definitions. A fuzzy logic-based analysis can permit the classification and tracking of brain states in a non-subjective and unsupervised manner. In this thesis, the combination of fuzzy c-means (FCM) clustering, wavelet, and information theory has revealed notable frequency features in epilepsy and anaesthetic-induced unconsciousness. It was shown that entropy changes in membership functions correlate to specific epileptiform activity and changes in anaesthetic dosages. Seizure episodes appeared in the 31-39 Hz band, suggesting changes in cortical functional organization. The induction of anaesthetics appeared in the 64-72 Hz band, while the return to consciousness appeared in the 32-40 Hz band. Changes in FCM activity were associated with the concentration of anaesthetics. These results can help with the treatment of epilepsy and the safe administration of anaesthesia.

Transitions between normal and pathological brain states are manifested differently in the electroencephalogram (EEG). Traditional discrimination of these states is often subject to bias and strict definitions. A fuzzy logic-based analysis can permit the classification and tracking of brain states in a non-subjective and unsupervised manner. In this thesis, the combination of fuzzy c-means (FCM) clustering, wavelet, and information theory has revealed notable frequency features in epilepsy and anaesthetic-induced unconsciousness. It was shown that entropy changes in membership functions correlate to specific epileptiform activity and changes in anaesthetic dosages. Seizure episodes appeared in the 31-39 Hz band, suggesting changes in cortical functional organization. The induction of anaesthetics appeared in the 64-72 Hz band, while the return to consciousness appeared in the 32-40 Hz band. Changes in FCM activity were associated with the concentration of anaesthetics. These results can help with the treatment of epilepsy and the safe administration of anaesthesia.

O autor aborda a conformidade das execuções fiscais de anuidades aos princípios do Devido Processo Legal e da Capacidade Contributiva, especialmente após o advento da Lei nº 12.514/2011, que alterou a definição do fato gerador da Contribuição devida aos Conselhos de Fiscalização Profissional. Valendo-se de pesquisa jurisprudencial sobre a forma como vêm sendo utilizados os meios para salvaguardar os créditos tributários, a presente dissertação questiona os parâmetros adotados para o deferimento de penhoras eletrônicas no âmbito destas execuções, considerando as peculiaridades da constituição do crédito tributário e da extração do título executivo pelas diversas projeções regionais dos Conselhos de Fiscalização. Com base no postulado da razoabilidade, apresenta critérios alternativos aptos a mitigar o caráter confiscatório da ordem de bloqueio e proteger o mínimo existencial dos executados, minimizando o risco de indisponibilidade de valores diretamente comprometidos com despesas de alimentação, saúde e moradia. / The author discusses the compliance of the procedure prior to tax foreclosure to the Due Process of Law and Contributory Capacity, especially after the advent of Law 12.514/2011, which changed the definition of the taxable event of the contribution due to the Supervisory Boards of Professional Activity. Drawing on jurisprudential research on how has been used the tools to safeguard the tax credits, the author also analyzes the parameters that have been used for the acceptance of electronic attachment under these executions, considering the peculiarities of the constitution of the tax credit and the extraction of the enforcement by the various projections of regional councils. Based on the postulate of reasonableness, the author presents alternative proposals able to mitigate the confiscatory nature of the freezing order and protect the vital minimum of the debtors, minimizing the risk of embrancing amounts directly committed to food expenses, health and housing.

In this work, we propose an approach that allows to explore the potential pathophysiological mechanisms (at neuronal population level) of ictogenesis by combining clinical intracranial electroencephalographic (iEEG) recordings with a neural mass model. IEEG recordings from temporal lobe epilepsy (TLE) patients around seizure onset were investigated. Physiologically meaningful parameters (average synaptic gains of the excitatory, slow and fast inhibitory population, Ae, B and G) were identified during interictal to ictal transition. We analyzed the temporal evolution of four ratios, i.e. Ae/G, Ae/B, Ae/(B + G), and B/G. The excitation/inhibition ratio increased around seizure onset and decreased before seizure offset, suggesting the disturbance and restoration of balance between excitation and inhibition around seizure onset and before seizure offset, respectively. Moreover, the slow inhibition may have an earlier effect on the breakdown of excitation/inhibition balance. Results confirm the decrease in excitation/inhibition ratio upon seizure termination in human temporal lobe epilepsy, as revealed by optogenetic approaches both in vivo in animal models and in vitro. We further explored the distribution of the average synaptic gains in parameter space and their temporal evolution, i.e. the path through the model parameter space, in TLE patients. Results showed that the synaptic gain values located roughly on a plane before seizure onset, dispersed during ictal and returned when the seizure terminated. Cluster analysis was performed on seizure paths and demonstrated consistency in synaptic gain evolution across different seizures from individual patients. Furthermore, two patient groups were identified, each one corresponding to a specific synaptic gain evolution in the parameter space during a seizure. Results were validated by a bootstrapping approach based on comparison with random paths. The differences in the path revealed variations in EEG dynamics for patients despite showing an identical seizure onset pattern. Our approach may have the potential to classify the epileptic patients into subgroups based on different mechanisms revealed by subtle changes in synaptic gains and further enable more robust decisions regarding treatment strategy. The increase of excitation/inhibition ratios, i.e. Ae/G, Ae/B and Ae/(B+G), around seizure onset makes them potential cues for seizure detection. We explored the feasibility of a model based seizure detection algorithm. A simple thresholding method was employed. We evaluated the algorithm against the manual scoring of a human expert on iEEG samples from patients suffering from different types of epilepsy. Results suggest that Ae/(B+G), i.e. excitation/(slow + fast inhibition) ratio, allowed the best performance and that the algorithm best suited TLE patients. Leave-one-out cross-validation showed that the algorithm achieved 94.74% sensitivity for TLE patients. The median false positive rate was 0.16 per hour, and median detection delay was -1.0 s. Of interest, the values of the threshold determined by leave-one-out cross-validation for TLE patients were quite constant, suggesting a general excitation/inhibition balance baseline in background iEEG among TLE patients. Such a model-based seizure detection approach is of clinical interest and could also achieve good performance for other types of epilepsy provided that more appropriate model, i.e. better describe epileptic EEG waveforms for other types of epilepsy, is implemented. Altogether, this thesis contributes to the field of epilepsy research from two perspectives. Scientifically, it gives new insights into the mechanisms underlying interictal to ictal transition, and facilitates better understanding of epileptic seizures. Clinically, it provides a tool for reviewing EEG data in a more efficient and objective manner and offers an opportunity for on-demand therapeutic devices. / Doctorat en Sciences de l'ingénieur et technologie / info:eu-repo/semantics/nonPublished

The goal of this research was to determine the procedures used for conducting a search and seizure in a tax-related offence in terms of the Criminal Procedure Act, Act 51 of 1977. Aspects that cause problems for the South African Revenue Service (SARS) investigators are the application for a search warrant and the activities that take place before, during and after the search and seizure. An introduction, definition and explanation are given of certain key concepts such as forensic and criminal investigations, as well as their objectives and purpose. The various search methods are also discussed and explained as are the chain of custody and evidence in general. A large part of this research deals with the legal requirements for a search and seizure in a tax-related offence and encompasses issues such as the procedures for obtaining a search warrant, pre-raid briefing, conducting the search, and the seizing of, marking, storage and disposal of documents. The findings of the research are discussed and recommendations subsequently made regarding the shortcomings identified. The findings that were made related to the process and procedure to obtain a search warrant, the actual execution of a search and seizure and the legislation that authorises searches and seizures in taxrelated offences. Further findings were made in respect of the mandate of SARS criminal investigators to investigate, the admissibility of evidence obtained from a search and seizure and the marking, recording, storage and disposal of seized items. Recommendations were made regarding training, improved communication and skills transfer to address the shortcomings identified. / Police Practice / (M.Tech. (Forensic investigation))

O autor aborda a conformidade das execuções fiscais de anuidades aos princípios do Devido Processo Legal e da Capacidade Contributiva, especialmente após o advento da Lei nº 12.514/2011, que alterou a definição do fato gerador da Contribuição devida aos Conselhos de Fiscalização Profissional. Valendo-se de pesquisa jurisprudencial sobre a forma como vêm sendo utilizados os meios para salvaguardar os créditos tributários, a presente dissertação questiona os parâmetros adotados para o deferimento de penhoras eletrônicas no âmbito destas execuções, considerando as peculiaridades da constituição do crédito tributário e da extração do título executivo pelas diversas projeções regionais dos Conselhos de Fiscalização. Com base no postulado da razoabilidade, apresenta critérios alternativos aptos a mitigar o caráter confiscatório da ordem de bloqueio e proteger o mínimo existencial dos executados, minimizando o risco de indisponibilidade de valores diretamente comprometidos com despesas de alimentação, saúde e moradia. / The author discusses the compliance of the procedure prior to tax foreclosure to the Due Process of Law and Contributory Capacity, especially after the advent of Law 12.514/2011, which changed the definition of the taxable event of the contribution due to the Supervisory Boards of Professional Activity. Drawing on jurisprudential research on how has been used the tools to safeguard the tax credits, the author also analyzes the parameters that have been used for the acceptance of electronic attachment under these executions, considering the peculiarities of the constitution of the tax credit and the extraction of the enforcement by the various projections of regional councils. Based on the postulate of reasonableness, the author presents alternative proposals able to mitigate the confiscatory nature of the freezing order and protect the vital minimum of the debtors, minimizing the risk of embrancing amounts directly committed to food expenses, health and housing.

Em tempos correntes, importantes processos de comunicação (escrita ou verbal) e armazenamento de informações aperfeiçoam-se por intermédio dos meios eletrônicos. À medida que o acesso à rede mundial de computadores (internet) se intensifica em progressões geométricas, multiplicam-se também os dados intercambiados por internautas e emergem técnicas cada vez mais avançadas de coleta e processamento de informações. Atividades rotineiras como a navegação e o envio de mensagens eletrônicas realizam-se apenas à custa de imenso trânsito de informações; como pegadas deixadas pelo caminho, os dados comutados nestas atuações permitem reconstituir os caminhos e atividades empreendidos na rede. A salvaguarda destas informações afigura-se imprescindível à vida privada e demanda rígida disciplina normativa. Não se trata apenas de impedir que dados de tráfego ou de conteúdo sejam empregados contrariamente ao Direito, mas de assegurar também que, em situações excepcionais descritas pelo legislador, sirvam para corroborar investigações criminais. Pretende-se neste trabalho um exame sistemático dos principais meios de busca da prova digital, com o escopo de delimitar o regime jurídico das intervenções nas comunicações eletrônicas e das medidas de apreensão de dados automatizados. Neste mister, inafastável analisar a disciplina constitucional do sigilo da comunicação de dados (CF, art. 5o, inciso XII) e investigar o fundamento legal das autorizações judiciais para a obtenção de informações eletrônicas. Sob perspectiva eminentemente interdisciplinar, cumpre discorrer sobre noções de Cibernética, telecomunicações, Informática, liberdade como autonomia recíproca de acesso à informação e comunicações eletrônicas, imprescindíveis à compreensão deste novo espaço do agir humano: o entorno digital. No campo da hermenêutica constitucional, necessário perquirir relevantes aspectos da vida privada e da proteção da intimidade antecedentes históricos, direito à privacy, hodierna projeção como autodeterminação informativa, teoria das três esferas e inviolabilidade das comunicações que permitirão opinar sobre a constitucionalidade das interceptações de dados em processos informacionais. Em sequência, devem ser conceituados os dados digitais e suas respectivas categorias, as técnicas de investigação penal e o resguardo de fontes de provas digitais. Sem deixar de contribuir para o aperfeiçoamento da normativa legal vigente, de rigor o exame de duas ordens distintas de incorporação dos dados ao processo: a intervenção no fluxo comunicativo destinada a captar dados e a apreensão física do dispositivo informático que alberga as informações. Como meios de busca de prova, esses procedimentos devem ser estudados de maneira individualizada, a partir de aspectos como conceito, regulação, natureza jurídica, finalidade, condicionantes legais (pressupostos, requisitos e limites), direito de defesa, juízo de proporcionalidade e controle. Por fim, tecidas as necessárias considerações sobre a conservação, eficácia probatória e valoração dos conteúdos automatizados, impõe-se indagar acerca dos efeitos decorrentes de operações ilícitas perpetradas sobre dados digitais. / In these days, important communication process (written or verbal) and information storage improve through electronic means. While the access to the computer worldwide web (internet) grows in geometrical progression, it also increases the number of webusers data and more and more advanced technics of gathering and processing information emerge. Routine activities such as sailing or sending electronic messages only happen due to the vast transit of information; like footprints left on the way, the data commutated in these actions allow to re-establish the ways and activities undertaken in the web. The security of these information figures indispensable to private life and demands a severe normative discipline. It is not only a matter of preventing that traffic or contents data may be used against the law. But also to assure that, in exceptional situation described by the legislator, it can be useful to confirm criminal investigation. This work intends a systematic examination of the main ways of searching digital evidence, with the purpose of delimitate the judiciary system of the intervention in electronic and apprehension extent of automation data. So, it must be analysed the constitutional discipline of communication data secrecy (CF, art. 5º, inciso XII) and even to investigate the legal foundation of judicial authorization to obtain electronic information. Under a strictly multidiscipline perspective, one must consider some notions of Cybernetics, telecommunication, Informatics, freedom as reciprocal autonomy access to electronic information and communication, which are essential to understand this new area of human act; the digital place. In the field of constitutional interpretation of law, it is necessary to scrutinize considerable aspects of private life and intimacy protection historical antecedents, privacy right, actual projection such as informative selfdetermination, three sphere theory and inviolability of communication so that they will permit to express an opinion about the constitutionality of interception data in informative proceedings. Sequentially, conceptualize the digital data and their respective categories, penal investigation technics and the protection of digital evidence sources. There may be a cooperation to a better improvement of the effective legal normative, an accurate examination of two different disposition of data incorporation to the process, the intervention in the communicative flow just to receive data and physical apprehension of the informatic device which contains information. As a quest in resources of proof, these proceedings must be examined in a individual way, starting with the aspects such as concept, regulation, juridical nature, finality, legal conditioning (presupposed, requisite and limits), right of defence, judgement of proportionality and control. At last, taken into everything about the conservation, evidential efficiency and the value of automatize contents still we have to enquire about the results of illicit operations perpetrated on digital data.

As crises não epilépticas psicogênicas (CNEP) podem ser definidas como episódios de alteração de movimentos, sensações ou experiência similar à epilepsia causada por processo psicológico e sem associação com descarga elétrica cerebral anormal. Estima-se que o número de casos de pacientes com CNEP seja de 2 a 33 por 100.000 habitantes. O índice de CNEP corresponde ainda a aproximadamente 5% dos pacientes tratados como epilépticos. Os pacientes com CNEP são tratados como possuindo epilepsia refratária, chegando ao limite máximo do tratamento medicamentoso e sem a obtenção de resultados satisfatórios. Objetivos: relatar os efeitos do tratamento psicanalítico individual em pacientes com CNEP. Método: A casuística foi composta por 37 pacientes com diagnóstico prévio de CNEP realizado por meio da monitorização por vídeo-EEG. Foram realizadas sessões individuais de tratamento psicanalítico, com frequência semanal, com duração aproximada de 50 minutos e duração total de 48 sessões em 12 meses. Resultados: Este estudo constatou elevado índice de sucesso no tratamento dos pacientes com CNEP: 29,7% (n=11) de cessação/cura dos sintomas e 51,4% (n=19) redução das crises convulsivas. Foi constatada associação entre cessar ou reduzir as crises e sexo (p < 0,01), religião (p < 0,01) e término do tratamento (p < 0,01). Conclusão: Este estudo apontou a eficácia do tratamento psicanalítico individual realizado com pacientes com CNEP, podendo ser considerada uma forma de assistência essencial para que haja decréscimo ou cessação das crises. / Psychogenic non-epileptic seizures (PNES) can be defined as episodes of alteration of movement, feeling or a similar experience to epilepsy caused by a psychological process and with no association with abnormal electrical discharges in the brain. It is estimated that the number of cases of patients with CNEP is from 2 to 33 in 100.000 inhabitants. The number of patients with PNES reaches 5% of those treated as epileptics. Patients with PNES are treated as if they had intractable epilepsy, with unsatisfactory results even after medication treatment is used to its maximum limits. Objectives: to present the effects of individual psychoanalytical treatment in patients with PNES. Methods: The case base was composed of 37 patients with PNES. The diagnosis was reached with video-EEG monitoring. . Psychoanalytical treatment was carried out through 12 months of weekly sessions of around 50-minutes each, in a total of 48 individual sessions. Results: This study found a high success rate in the treatment of PNES patients. 29,7% (n=11) of patients saw cessation or cure of symptoms and 51,4% (n=19) saw a decrease in the number of episodes. There is an association between cessation or decrease in the number of episodes and sex (p < 0,01), religion (p < 0,01) and concluding treatment (p < 0,01). Conclusions: Individual psychoanalytical treatment applied to patients with PNES is considered effective and can be considered as an essential form of assistance for the reduction of cessation of episodes. Psychogenic non-epileptic seizures, Conversion disorder, Psychoanalysis, Treatment

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Epilepsy is a syndrome characterized by spontaneous recurrent seizures, result of paroxys-mal discharges , excessive or synchronous a neural population . Despite the good prognosis, the high number of patients with epilepsy who have seizures refractory to medication, reflects the lack of a bet-ter understanding of excitotoxic disorders characteristic of this disease. Thus, it becomes important to understand the mechanisms for induction and maintenance of seizures as well, the search for new antiepileptic compounds that may prevent the development of this pathology. As nociception and epi-lepsy have mechanisms in common and several anticonvulsant drugs are used in treatment of pain , we investigated the effect of triterpene 3β , 6β , 16β Trihidroxilup -20 ( 29) -ene (TTHL), a compound with antinociceptive properties in convulsions induced by pentylenetetrazol (PTZ). The TTHL admin-istration ( 30 mg / kg , po) increased the latency to the first myoclonic seizures and tonic- clonic sei-zure and decreased the duration of generalized seizures induced by PTZ . In addition , the administra-tion of TTHL reduced lipid peroxidation and protein carbonylation , as well as protected from inhibition of glutamate uptake and activity of the Na+, K+-ATPase (α1and α2/α3 subunits ) caused by PTZ . Alt-hough the TTHL showed no antioxidant activity per se and not alter the binding of [ 3H ] flunitrazepam to the site of the GABAA receptor bezodiazepínico , this protected compound of convulsions and inhi-bition of Na+, K+-ATPase activity induced by ouabain . These results suggest that the anticonvulsant action is due TTHL s maintenance of Na+, K+-ATPase . In fact , the experiments performed in the cer-ebral cortex in vitro showed that PTZ ( 10 mM ) reduced the activity of Na+, K+-ATPase and that prein-cubation with TTHL ( 10 mM ) protected from this inhibition.Thus , these data indicate that the protec-tion exerted by TTHL this seizure model is not related to antioxidant activity or GABAergic activity . However, these results demonstrate that effective protection of Na+, K+-ATPase activity induced by this compound protects against oxidative and excitotoxic damage induced by PTZ . / A epilepsia é uma síndrome caracterizada por crises espontâneas e recorrentes, resultado de descargas paroxísticas, excessivas e sincrônicas de uma população neural. Apesar do bom prognós-tico, o elevado número de pacientes com epilepsia, que apresentam convulsões refratárias aos medi-camentos, reflete a falta de um melhor entendimento dos distúrbios excitotóxicos característico desta doença. Desta forma, torna-se importante o entendimento dos mecanismos de indução e manuten-ção das convulsões, bem como, a busca por novos compostos anticonvulsivantes que possam evitar o desenvolvimento desta patologia. Como a nocicepção e a epilepsia possuem mecanismos em co-mum, e vários anticonvulsivantes são usados no tratamento da dor, foi investigado o efeito do Triter-peno 3β,6β,16β Trihidroxilup-20(29)-eno (TTHL), um composto com propriedades antinociceptivas, nas convulsões induzidas pelo pentilenotetrazol (PTZ). A administração do TTHL (30 mg/kg; p.o) au-mentou a latência para a primeira convulsão mioclônica e tônico-clônica e reduziu a duração das convulsões generalizadas induzidas pelo PTZ. Além disso, a administração do TTHL reduziu a pero-xidação lipídica e a carbonilação de proteínas, assim como, protegeu da inibição da captação de glu-tamato e da atividade da Na+,K+-ATPase (subunidades α1 e α2/α3) causadas pelo PTZ. Embora, o TTHL não mostrou uma atividade antioxidante per se e não alterou a ligação do [3H]flunitrazepam ao sítio para bezodiazepínico do receptor GABAA, este composto protegeu das convulsões e da inibição da atividade da Na+, K+- ATPase induzidos pela ouabaina. Estes resultados sugerem que a ação an-ticonvulsivante do TTHL é devido s manutenção da atividade da Na+,K+-ATPase. De fato, os experi-mentos realizados no córtex cerebral in vitro mostraram que o PTZ (10 mM) reduziu a atividade da Na+,K+-ATPase e que a incubação prévia com TTHL (10 μM) protegeu desta inibição. Dessa forma, estes dados indicam que a proteção exercida pela TTHL neste modelo de convulsão não está relaci-onado com atividade antioxidante ou a atividade GABAérgica. No entanto, estes resultados demons-traram que a proteção eficaz da atividade da Na+,K+-ATPase , induzida por este composto, protege contra os danos excitotóxic e oxidativos induzidos pelo PTZ.