Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal

Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. It is characterized by a progressive occurrence of epileptic seizures originating in the temporal lobe, particularly in the hippocampal formation (mesial TLE). Among the animal models used to investigate the physiopathologic...

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Autor principal:	Bessa, Rafael dos Santos de
Outros Autores:	Pereira, Rodrigo Neves Romcy
Formato:	Dissertação
Idioma:	por
Publicado em:	Brasil
Assuntos:	Epilepsia do lobo temporal Status Epilepticus Ácido caínico Pilocarpina Eletrofisiologia Hipocampo CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
Endereço do item:	https://repositorio.ufrn.br/jspui/handle/123456789/24080
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id	ri-123456789-24080
record_format	dspace
institution	Repositório Institucional
collection	RI - UFRN
language	por
topic	Epilepsia do lobo temporal Status Epilepticus Ácido caínico Pilocarpina Eletrofisiologia Hipocampo CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
spellingShingle	Epilepsia do lobo temporal Status Epilepticus Ácido caínico Pilocarpina Eletrofisiologia Hipocampo CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS Bessa, Rafael dos Santos de Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
description	Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. It is characterized by a progressive occurrence of epileptic seizures originating in the temporal lobe, particularly in the hippocampal formation (mesial TLE). Among the animal models used to investigate the physiopathological mechanisms of TLE, the most used are those that lead to spontaneous seizures after an initial insult, such as a prolonged convulsive state (status epilepticus, SE). This condition can be induced by the administration of the glutamatergic agonist, kainic acid (KA) or the cholinergic agonist, pilocarpine (PILO). However, the use of systemic injections and the lack of electrophysiological monitoring during SE lead to high mortality rates, widespread cell death and high behavioral variability during the chronic phase of epilepsy, which differs in several aspects from the human condition. These effects are mainly due to the lack of electrographic control of SE duration and the dynamics of the epileptogenesis process during the weeks following SE. Therefore, this project aimed to generate two animal models of TLE by intra-hippocampal injections of KA or PILO, and then, to analyze their behavioral and electrographic progression during SE. It is important to notice that no electrophysiological study has investigated the SE dynamics in animals infused with PILO into hippocampus so far. For that, we implanted two bundles of microelectrodes in the hippocampus bilaterally, one bundle in the medial prefrontal cortex and a cannula above the intermediate hippocampus for KA or PILO infusion. Following SE induction, we analyzed the behavioral and electrophysiological evolution of KA and PILO animals. SE was blocked after 2h by the injection of an anti-convulsant cocktail and the animals were continuously monitored by video-EEG for up to 72h. Seven days after SE, animals underwent euthanasia and had the brains removed for histological localization of cannula and electrodes. Video and EEG recordings were analyzed by visual inspection and spectral decomposition. Our results showed that PILO animals had shorter latency for first behavioral seizure than KA rats after drug injection. However, seizure severity showed higher variability among PILO rats (PILO: 50% animals had class 3 or higher vs. KA: 90% animals had class 1; Racine’s scale). PILO animals had a reduced number of wet-dog shake behaviors and shorter latency to SE onset as compared to KA rats. Electrophysiologically, we observed that high frequency oscillations (>150 Hz) occurred short after the injection of both drugs (15-40min before SE onset), as opposed to what is commonly reported to occur during the chronic phase of epilepsy in rodents. They were usually found within the first electrographic seizures. Finally, we have identified a distinct modular organization of paroxystic activity during the SE in each group, which consisted of blocks of nested rhythms. These findings thus suggest that PILO is more epileptogenic that KA and that these drugs produce distinct SE dynamics, which seem to be organized as periodically repeating modules of nested oscillations, modules of hyper synchrony with no nested oscillations and segments of asynchronous activity. Our data emphasizes the importance to conduct electrophysiological recordings during SE induction in order to better control individual brain responses. This can reduce variability during epileptogenesis and produce a more homogeneous model of chronic epilepsy.
author2	Pereira, Rodrigo Neves Romcy
author_facet	Pereira, Rodrigo Neves Romcy Bessa, Rafael dos Santos de
format	masterThesis
author	Bessa, Rafael dos Santos de
author_sort	Bessa, Rafael dos Santos de
title	Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
title_short	Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
title_full	Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
title_fullStr	Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
title_full_unstemmed	Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
title_sort	dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal
publisher	Brasil
publishDate	2017
url	https://repositorio.ufrn.br/jspui/handle/123456789/24080
work_keys_str_mv	AT bessarafaeldossantosde dinamicadostatusepilepticusemdoismodelosanimaisdeepilepsiadolobotemporal
_version_	1773966944326647808
spelling	ri-123456789-240802022-04-05T22:06:51Z Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal Bessa, Rafael dos Santos de Pereira, Rodrigo Neves Romcy http://lattes.cnpq.br/6313181480655294 http://lattes.cnpq.br/9209418339421588 Queiroz, Cláudio Marcos Teixeira de http://lattes.cnpq.br/3384801391828521 Belchior, Hindiael Aeraf http://lattes.cnpq.br/2815729240392635 Leite, João Pereira http://lattes.cnpq.br/5191541542901913 Epilepsia do lobo temporal Status Epilepticus Ácido caínico Pilocarpina Eletrofisiologia Hipocampo CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. It is characterized by a progressive occurrence of epileptic seizures originating in the temporal lobe, particularly in the hippocampal formation (mesial TLE). Among the animal models used to investigate the physiopathological mechanisms of TLE, the most used are those that lead to spontaneous seizures after an initial insult, such as a prolonged convulsive state (status epilepticus, SE). This condition can be induced by the administration of the glutamatergic agonist, kainic acid (KA) or the cholinergic agonist, pilocarpine (PILO). However, the use of systemic injections and the lack of electrophysiological monitoring during SE lead to high mortality rates, widespread cell death and high behavioral variability during the chronic phase of epilepsy, which differs in several aspects from the human condition. These effects are mainly due to the lack of electrographic control of SE duration and the dynamics of the epileptogenesis process during the weeks following SE. Therefore, this project aimed to generate two animal models of TLE by intra-hippocampal injections of KA or PILO, and then, to analyze their behavioral and electrographic progression during SE. It is important to notice that no electrophysiological study has investigated the SE dynamics in animals infused with PILO into hippocampus so far. For that, we implanted two bundles of microelectrodes in the hippocampus bilaterally, one bundle in the medial prefrontal cortex and a cannula above the intermediate hippocampus for KA or PILO infusion. Following SE induction, we analyzed the behavioral and electrophysiological evolution of KA and PILO animals. SE was blocked after 2h by the injection of an anti-convulsant cocktail and the animals were continuously monitored by video-EEG for up to 72h. Seven days after SE, animals underwent euthanasia and had the brains removed for histological localization of cannula and electrodes. Video and EEG recordings were analyzed by visual inspection and spectral decomposition. Our results showed that PILO animals had shorter latency for first behavioral seizure than KA rats after drug injection. However, seizure severity showed higher variability among PILO rats (PILO: 50% animals had class 3 or higher vs. KA: 90% animals had class 1; Racine’s scale). PILO animals had a reduced number of wet-dog shake behaviors and shorter latency to SE onset as compared to KA rats. Electrophysiologically, we observed that high frequency oscillations (>150 Hz) occurred short after the injection of both drugs (15-40min before SE onset), as opposed to what is commonly reported to occur during the chronic phase of epilepsy in rodents. They were usually found within the first electrographic seizures. Finally, we have identified a distinct modular organization of paroxystic activity during the SE in each group, which consisted of blocks of nested rhythms. These findings thus suggest that PILO is more epileptogenic that KA and that these drugs produce distinct SE dynamics, which seem to be organized as periodically repeating modules of nested oscillations, modules of hyper synchrony with no nested oscillations and segments of asynchronous activity. Our data emphasizes the importance to conduct electrophysiological recordings during SE induction in order to better control individual brain responses. This can reduce variability during epileptogenesis and produce a more homogeneous model of chronic epilepsy. A epilepsia do lobo temporal (ELT) é a forma mais frequente de epilepsia em adultos, caracterizada clinicamente por um quadro progressivo de crises epilépticas com foco no lobo temporal, em particular no hipocampo. Dentre os modelos animais, os mais utilizados na investigação dos mecanismos fisiopatológicos desta condição geram crises recorrentes espontâneas através da indução inicial de um estado convulsivo sustentado (status epilepticus, SE) – por administração do agonista glutamatérgico ionotrópico, ácido caínico (AC) ou do agonista colinérgico muscarínico, pilocarpina (PILO). Entretanto, o uso de injeções sistêmicas e a falta de controle preciso sobre a duraçãodo SE geram alta mortalidade, morte celular dispersa e grande variabilidade comportamental durante a fase crônica da epilepsia, o que difere em vários aspectos do quadro humano. A nosso ver, este padrão decorre da ação sistêmica da droga e da dificuldade de controlar a atividade eletrográfica/tempo de SE a que cada animal é submetido, influenciando a dinâmica da epileptogênese. Portanto, este projeto teve como objetivo gerar modelos de ELT por infusão intra-hipocampal de AC e PILO em ratos e analisar seus comportamentos e atividade eletrofisiológica durante o SE. Vale ressaltar que ainda não há estudos eletrofisiológicos aprofundados sobre o modelo de PILO intra-hipocampal. Para isto, implantamos feixes de microeletrodos bilateralmente no hipocampo e unilateralmente no córtex pré-frontal medial (CPFm), junto a uma cânula no hipocampo ventral para infusão de AC ou PILO. Após a indução do SE analisamos a progressão comportamental e eletrofisiológica dos animais. O SE foi bloqueado após 2h por um coquetel anti-convulsivante mais potente do que o utilizado na maioria dos estudos atuais e os animais foram acompanhados por registros contínuos de vídeo-EEG sincronizado por até 72h. Sete dias após o SE, os animais foram sacrificados e seus cérebros retirados para verificação histológica da posição da cânula e eletrodos. Os registros de vídeo e de EEG foram analisados por inspeção visual e técnicas de análise de séries temporais. Nossos resultados mostraram que os animais PILO apresentam 1a crise comportamental com menor latência do que os animais tratados com AC, porém com severidade mais variável (AC: 90% animais classe 1 vs. PILO: 50% animais ≥classe 3, escala de Racine). Animais PILO também tiveram menor número de comportamentos do tipo wet-dog shakes que os animais AC, associado a um início de SE precoce comparado aos animais AC. Do ponto de vista eletrofisiológico, observamos oscilações de alta frequência (>150 Hz), comumente observadas na fase crônica da epilepsia, logo após a injeção de ambos convulsivantes (15-40 min antes do início do SE) concomitante às primeiras crises eletrográficas. Por fim, identificamos que o SE em ambos modelos exibe uma organização modular da atividade paroxística com vários níveis de ritmicidade sobrepostos. Nossos resultados indicam uma maior epileptogenicidade da PILO em relação ao AC e, que estas drogas produzem SE com dinâmicas distintas. Pudemos observar uma composição com módulos de oscilações sobrepostas repetidos periodicamente, módulos de hipersincronia sem oscilações acopladas e segmentos de atividade assíncrona. Nossos dados ressaltam a importância do registro eletrográfico durante o SE para melhor controlar as respostas individuais durante este período. 2017-10-16T20:46:40Z 2017-10-16T20:46:40Z 2016-08-30 masterThesis BESSA, Rafael dos Santos de. Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal. 2016. 88f. Dissertação (Mestrado em Neurociências) - Universidade Federal do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, 2016. https://repositorio.ufrn.br/jspui/handle/123456789/24080 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM NEUROCIÊNCIAS

Dinâmica do status epilepticus em dois modelos animais de epilepsia do lobo temporal

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