Environmental air pollution is an aggravating event for sudden unexpected death in epilepsy / Exposicao ambiental a poluicao do ar e um evento agravante para a ocorrencia de morte subita nas epilepsias

It is extremely difficult to estimate the occurrence of sudden unexpected death in epilepsy (SUDEP). On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with refractory epilepsy may prevent fatal events in these individuals. In this context, we should not ignore that urban air pollution is a leading problem for environmental health and is able to cause serious cardiovascular dysfunctions that culminate in sudden death. In this regard, we aimed to determine whether environmental exposure to air pollution is an aggravating event for SUDEP.

É extremamente difícil estimar a ocorrência de morte súbita em epilepsia (SUDEP). Por outro lado, detectar e avaliar cuidadosamente novos factores de risco que podem contribuir para o aparecimento de alterações cardiovasculares em pessoas com epilepsia refratária poderá ser capaz de impedir a ocorrência de eventos fatais nestes indivíduos. Neste contexto, não devemos negligenciar hoje que a poluição do ar nas grandes cidades é um problema para a saúde ambiental, podendo causar graves disfunções cardiovasculares, que culminam em morte súbita. Neste sentido, propusemos nesse trabalho que a exposição ambiental a poluição do ar é um evento agravante para a ocorrência de SUDEP.

The pilocarpine model of epilepsy: what have we learned?

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.

A administração sistêmica do potente agonista muscarínico pilocarpina em ratos promove alterações comportamentais e eletrográficas que podem ser divididas em três períodos distintos: (a) período agudo o animal evolui progressivamente para o status epilepticus, que perdura por até 24h; (b) período silencioso, caracterizado pela normalização progressiva do comportamento e do EEG e pode ter uma duração de 4 a 44 dias; período crônico, aparecimento de crises epilépticas espontâneas e recorrentes (SRSs). As características das SRSs observadas nos animas durante o período crônico são semelhantes às crises parciais complexas dos seres humanos e recorrem de 2-3 vezes por semana/animal. Além disso, o modelo de epilepsia induzido pela pilocarpina é válido não somente para se estudar a patogênese da epilepsia do lobo temporal em humanos como também para se testar a viabilidade de drogas antiepilépticas. Esse artigo de revisão aborda diversos aspectos do modelo de epilepsia induzido pela pilocarpina.

Could sudden cardiac death in epilepsy be related to the occurrence of thalamic dysfunction or anatomic change? / A morte súbita cardíaca em epilepsia poderia estar relacionada com a ocorrência de alterações anatômicas ou funcionais do tálamo?

Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death in people with chronic epilepsy. Its physiopathology is still unknown; however, the most commonly suggested potential mechanisms involve cardiac or respiratory abnormalities. As the anatomical substrate of epileptic activity in the central nervous system (CNS) shows a direct relationship with cardiovascular alterations, this may suggests that patients with epilepsy associated with focal CNS lesions may be at particular risk of SUDEP. Currently, experimental and clinical data support an important role for thalamic nuclei in the behavioural manifestations, initiation and propagation of seizures. In view of the above findings, we purpose that SUDEP, at least in some cases, could be related to the occurrence of thalamic dysfunction or anatomic change.

A morte súbita e inesperada nas epilepsias (SUDEP) é a mais importante causa de morte em pacientes com epilepsia. A fisiopatologia da SUDEP ainda é desconhecida, no entanto, os prováveis mecanismos estão relacionados com alterações cardiovasculares ou respiratórias. Como o substrato anatômico da atividade epiléptica no sistema nervoso central (SNC) apresenta direta relação com alterações cardiovasculares, esse fato sugere que pacientes com epilepsia e lesões focais no SNC podem apresentar maior risco para SUDEP. Atualmente, dados experimentais e clínicos demonstram um importante papel dos núcleos talâmicos nas manifestações comportamentais, bem como no início e propagação das crises epilépticas. Sendo assim, nós acreditamos que a SUDEP, pelo menos em alguns casos, poderia estar relacionada com a ocorrência de alterações anatômicas ou disfunções talâmicas.

The contribution of the lateral posterior and anteroventral thalamic nuclei on spontaneous recurrent seizures in the pilocarpine model of epilepsy

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

Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

Status epilepticus (SE) is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6 percent), caudate-putamen (+30.6 percent), frontoparietal cortex (+32.2 percent), amygdala (+31.7 percent), entorrinal cortex (+28.2 percent), thalamic nucleus (+93.5 percent), pre-tectal area (+50.1 percent) and substantia nigra (+50.3 percent) when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus