Estudo das alterações do estado de mal epiléptico induzido por pilocarpina no cérebro de camundongos imunodeficientes BALB/c nude

• Ano de defesa: 2010
• Autor(a) principal: Vignoli, Thiago [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Morte Neuronal; BALB/c nude; Pilocarpina; Sistema imunológico; Epilepsia; Pilocarpine; Epilepsy; Immune System
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9542

Epilepsy affects about 1-2% of world population and lack of effective therapeutic interventions more effective. Approximately 30% are symptomatic of epilepsy and temporal lobe epilepsy (TLE) is distinguished by the high incidence and severity. About 30% of patients with TLE seizures are refractory to treatment, if necessary, often, surgical intervention for control of them. The investigation of pathophysiology mechanism using human tissue extracted surgically, although very important, is limited by reflects only the chronic process in which the molecular, biochemical, and neuronal plasticity alterations resulting from epileptic effects already established. Thus, experimental models are essential for better approach of the mechanisms involved in epileptogenesis. The epilepsy induced by pilocarpine in small rodents has been widely used for reproducing the main features of TLE. In this model, the seizures are accompanied by a combined action between immune system, nervous and endocrine systems, involving the mediators activation such as cytokines, chemokines, neurotransmitters and their cell receptors. These processes have been associated with the etiology of the epileptic condition. In this project, immunodeficient BALB/c nude mice submitted to epilepsy model induced by pilocarpine to characterize behavior, electrographic, histological and neurochemical changes compared to their control BALB/c. The results indicated that integrity of the immune system is necessary to protect the central nervous system insult caused by status epilepticus. After administration of pilocarpine, the BALB/c nude mice showed a larger number of tonic-clonic seizures, with a high mortality rate when compared to BALB/c. The BALB/c nude also showed a greater activation of c-Fos in areas related to the circuitry of the crisis and a lower expression of parvalbumin, an intracellular calcium-binding protein compared to BALB/c studied in the same experimental condition. Differences concentrations of excitatory and inhibitory neurotransmitters were also observed in cortex and hippocampus of the BALB/c nude compared to BALB/c. The BALB/c nude showed increased of the excitatory amino acids concentrations without compensatory alteration in the inhibitory amino acids during seizure, as occurred in BALB/c. Neuronal death measured by Fluoro Jade- B and Nissl histological techniques, was also increased in some areas of the central nervous system of BALB/c nude SE presented relative to BALB/c. The data suggest a positive correlation between c-Fos activation, excitatory amino acids concentration and neuronal death in BALB/c nude mice, suggesting that immune deficiency may have contributed to the hyperexcitability and vulnerability of the central nervous system injury caused by seizure.