Akt pathway activation and increased neuropeptide Y mRNA expression in the rat hippocampus: Implications for seizure blockade

The aim of this study was to analyze the expression of survival-related molecules such Akt and integrin-linked kinase (ILK) to evaluate Akt pathway activation in epileptogenesis process. Furthermore, was also investigated the mRNA expression of neuropeptide Y, a considered antiepileptic neuropeptide, in the pilocarpine-induced epilepsy. Male Wistar rats were submitted to the pilocarpine model of epilepsy. Hippocampi were removed 6 h (acute phase), 12 h (late acute), 5d (silent) and 60d (chronic) after status epilepticus (SE) onset, and from animals that received pilocarpine but did not develop SE (partial group). Hippocampi collected were used to specify mRNA expression using Real-Time PCR. Immunohistochemistry assay was employed to place ILK distribution in the hippocampus and Western blot technique was used to determine Akt activation level. A decrease in ILK mRNA content was found during acute (0.39 +/- 0.03) and chronic (0.48 +/- 0.06) periods when compared to control group (0.87 +/- 0.10). Protein levels of ILK were also diminished during both periods. Partial group showed increased ILK mRNA expression (0.80 +/- 0.06) when compared with animals in the acute stage. Silent group had ILK mRNA and immunoreactivity similar to control group. Western blot assay showed an augmentation in Akt activation in silent period (0.52 +/- 0.03) in comparison with control group (0.44 +/- 0.01). Neuropeptide Y mRNA expression increased in the partial group (1.67 +/- 0.22) and in the silent phase (1.45 +/- 0.29) when compared to control group (0.36 +/- 0.12). Results suggest that neuropeptide Y (as anticonvulsant) might act in protective mechanisms occurred during epileptic phenomena. Together with ILK expression and Akt activation, these molecules could be involved in hippocampal neuroprotection in epilepsy. (C) 2009 Elsevier B.V. All rights reserved.Univ Nove de Julho, Rehabil Sci Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Neurol Neurosurg Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Neurol Neurosurg Dept, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilWeb of Scienc

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.<br>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