Efeito do tratamento com brilhant blue G, um bloqueador do receptor P2X7, potencializado com células-tronco mesenquimais no hipocampo de animais epilépticos crônicos

• Ano de defesa: 2017
• Autor(a) principal: Moreira, Diego Marques [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: Epilepsy; Temporal lobe epilepsy; Mesenchymal stem cells; Purinergic receptor P2X7; Brilliant blue G; Hippocampus; Epilepsia; Epilepsia do lobo temporal; Células tronco mesenquimais; Receptores purinérgios P2X7; Hipocampo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5454113; http://repositorio.unifesp.br/handle/11600/49988

Epilepsy has as its main characteristic the manifestation of spontaneous and recurrent seizures that develop from neuronal changes in certain areas of the central nervous system. It has recently been shown that the P2X7 receptor (P2X7r) is overexpressed in the brain of chronic epileptic animals and in experimental models for various neurodegenerative diseases, supporting the hypothesis that P2X7 participates in pathways involved in neurodegeneration. In addition, blocking P2X7r with Brilliant Blue G (BBG), a P2X7r antagonist capable of crossing the blood-brain barrier, prevents the death of neural cells induced by status epilepticus (SE) in the epileptogenic phase Mesenchymal stem cells have paracrine properties, that is, they are able to release trophic factors that lead to a decrease in the inflammatory, apoptotic process and increase in cell proliferation at the injured site. Currently, the stem cell study has been suggested as possible treatments for neurodegenerative diseases, due to its ability to decrease neuroinflammatory processes and also due to its ability to differentiate in neurons. Thus, our work investigated the therapeutic potential of P2X7 receptor blockers, BBG, combined with mesenchymal stem cell transplantation in the chronic period of pilocarpine-induced epilepsy. This study contributed to the understanding of the mechanisms involved in hippocampal repair promoted by BBG and by mesenchymal stem cells in epilepsy. Adult male Wistar rats were treated with pilocarpine for an S.E. induction, and 14 days after recovery of substances subjected to stereotactic surgery for intrahippocampal MSC administration.After surgery, the rats were kept on observation for chronic seizures recording for 90 days, and treated with BBG from the 30th to the 60th day after SE (16 injections on interquartered days). As MSC donors were used by C57 / BL6EGFP mice All procedures were duly authorized by the institution's ethics committee under opinion # 8977 (Annex II). The results obtained in this study are the transplantation of MSC in epileptic rats, concomitantly with the treatment with BBG, to act in the preservation of cells and the reduction of seizures, thus indicating therapeutic potential.We conclude that the protective activity in the CTM-BBG group indicates that the decrease in inflammation in epilepsy is a critical piece for a reduction of seizures.The inflammatory mechanisms involved in epilepsy need to be better explo red.