Estudo do bloqueio do receptor adenosinérgico A2A no modelo experimental de epilepsia induzida por pilocarpina

• Ano de defesa: 2009
• Autor(a) principal: Rosim, Fernanda Elisa [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Epilepsia; Pilocarpina; Adenosina; Antagonista A2A; Agonista A; Modulação das crises; Neuroproteção; Epilepsy; Pilocarpine; Adenosine
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9559

Adenosine is an important endogenous neuromodulator with anticonvulsant and neuroprotective properties. The present work studied the effect of blocking the adenosinergic A2A receptor by selective antagonist SCH58261, associated or not, the activation of A1 receptor by agonist R-Pia in the seizures modulation and neuroprotection of the brain areas vulnerable to injury in the pilocarpine model. Eight groups were studied: Pilo, SCH+Pilo, RPia+ Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, RPia+ SCH+Saline. The behavioral parameters: number of animals that developed status epilepticus, latency to the beginning of SE and mortality rate after the insult were evaluated. Through the technique of FJ-B, evaluated the neurodegeneration and through the technique of immunohistochemistry, the caspase -1 expression in brain regions, 24 hours and 7 days after SE. The results showed that pre-treatment with SCH58261, R-Pia and the combination of both reduced the number of animals in SE, increased the threshold for the establishment of the SE and decreased the mortality rate after the insult, compared to pilocarpine treatment. The pre-treatment with R-Pia e R-Pia + SCH58261 reduces the intensity of marking by FJ-B in CA3, hilus of dentate gyrus and piriform cortex after 24 hours and 7 days of the SE, compared to pilocarpine treatment. The caspase -1 expression, 24 hours after the SE, was intense in the amygdala, and moderate in the piriform and entohrinal cortex and absent in the hippocampus, whereas, 7 days after SE, the expression was intense in the hippocampus and amygdala, discreet in the cortex entohrinal and moderate in the piriform cortex in all groups, except in the controls. We conclude that the A2A antagonist have potent anticonvulsant effect, but does not promote neuroprotection in brain areas vulnerable to injury, while the A1 agonist, has a crucial role in the modulation of seizures and promotes significant neuroprotection in the pilocarpine model.