EFEITO DO N-METIL-D-ASPARTATO (NMDA) EM CAMUNDONGOS SUBMETIDOS A MODELO DE EPILEPSIA POR PILOCARPINA

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Müller, Pricila Tolio
Orientador(a): Boeck, Carina Rodrigues
Banca de defesa: Silva, Rosane Souza da, Schuch, Natielen Jacques
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Franciscana
Programa de Pós-Graduação: Mestrado em Ciências da Saúde e da Vida
Departamento: Ciências da Saúde e da Vida
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/610
Resumo: Epilepsy is characterized by a cerebral disorder with interruptions, recurrent and unpredictable of normal brain function. Glutamate is the major excitatory neurotransmitter in the brain and is involved in the mechanism of status epilepticus - a prolonged and self-sustaining seizure. The drug N-methyl-D-aspartate (NMDA) is a synthetic excitotoxin that acts as a specific agonist for the NMDA receptor subtype of glutamate. Pre- and post-conditioning strategies provide a proposal for molecular mechanisms responsible for endogenous neuronal protection. The aim of the study is evaluating the effect of NMDA in different doses against damage following status epilepticus induced by pilocarpine in animal model of epilepsy. For this purpose, 210 adult male mice (60 days, 30-40 g) Swiss albino were treated intraperitoneally with pilocarpine (100 mg/kg every 20 min up to a maximum of 300 mg/kg) evoking status epilepticus. All animals were exposed to behavioral tasks for motor evaluation (locomotion, balance, motor coordination) and memory, followed by evaluation of cellular viability at 30 days post-pilocarpine. The pilocarpine death in approximately 40% of the mice during 24 hours. Treatment with lower doses of NMDA (18 mg/kg) prolonged survival time without change the outcome. The other NMDA doses also had no significant effect on the number of deaths. The status epilepticus caused reduction of the locomotor activity of the mice, an effect reversed by treatment with NMDA 37 mg/kg. The pilocarpine group mice did not show expressive cognitive deficit during acquisition of memory, however reduced evocation. Cellular viability assessed 30 days after status epilepticus indicated damage by MTT test, but not by propidium iodide. Only the 18 mg/kg NMDA reduced damage. It is concluded that the dose 18 mg/kg NMDA induced neuroprotection in surviving animals. The cellular mechanisms of NMDA-induced tolerance remain unknown, but the present study reinforces the dual NMDA effect, since the same dose that increased the mortality rate was able to reduce cellular damage.