Participação da progesterona e do estradiol na redução das crises convulsivas induzida pela gestação em um modelo genético de epilepsia.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

Pregnancy reduces the intensity of epileptic seizure in part of the population of a genetic model of reflex epilepsy in which seizures are induced by high intensity sound stimulation, the Wistar Audiogenic Rats (WAR), as it has been shown by previous studies of our lab. However, the mechanism involved in this reduction has not been yet clarified. Several studies show that progesterone (P) and its metabolites have anti-seizures effects and, in general, administration of estradiol (E) appears to exacerbate epilepsy. The aim of the present work was investigate the involvement of progesterone and estradiol in the seizure reduction induced by pregnancy in WAR. The severity index (SI) of seizure was determined during pregnancy and two sub-groups were compared: WAR displaying reduced severity index of seizure (RSI) with the subgroup that did not show any alteration of the severity index (non-reduced severity index, NRSI). In Experiment 1, Wistar and WAR rats were sacrificed at 7th, 14th, and 20th days of pregnancy and levels of estradiol and progesterone were measured in plasma by radioimmunoassay. On the 20th day of pregnancy, the seizures remitted in 50% of WAR, with 33% showing SI=0. The P and E levels were higher in the RSI group than in NRSI. Moreover, P/E ratio of RSI group was similar to the control, non epileptic rats, but this ratio was diminished in relation to the control in the NRSI group. To confirm the gonadal steroids participation in the seizure reduction, Wistar and WAR rats were ovariectomized (ovx) and separated in groups that received daily injections of different schedules of treatment with progesterone (500 µg; im) and/or estrogen (1g/100g, sc): a) vehicle (3 weeks); b) estrogen (3 weeks) plus progesterone (3 weeks); c) estrogen (1 week) followed by progesterone (2 weeks) or d) progesterone alone (3 weeks). When progesterone was administered alone, seizure reduction occurred in 33% of WAR, while progesterone with estrogen in both regimens reduced the audiogenic seizures in 67% of WAR. In conclusion, this work demonstrated an important role for the gonadal steroids, progesterone and estradiol, in seizure reduction in this genetically audiogenic susceptible strain of rats. Moreover, shows that estradiol is important to enhance the anti-seizure effects of progesterone.

ASSUNTO(S)

estradiol teses. fisiologia teses. epilepsia teses. progesterona teses. gravidez teses.

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