Estradiol alters afterdischarge threshold and acquisition of amygdala kindled seizures in male rats.
ABSTRACT We have previously shown that estradiol (E(2)) can initially increase and then decrease kindle seizure parameters in amygdala kindled male rats. This study focuses on the effects of estradiol benzoate (EB) on afterdischarge (AD) threshold and electrical kindling acquisition in intact male rats. After implantation of tripolar and monopolar electrodes in amygdala and dura surface respectively, effects of EB on AD threshold and electrical kindling acquisition were investigated by daily injection of EB (microg/kg) or sesame oil (EB solvent) in different groups of male rats. AD threshold was reduced significantly 0.25 h post EB treatment and reached to the lowest value after 24 h and remained almost constant at low values. Also, the number of trials for stage 5 (S(5)) and cumulative seconds of AD to complete kindling decreased significantly, when compared to rats without EB treatment. These results support a marked influence of E(2) on seizure process and convulsive pattern in the brain of male rats. Base on the previous reports about female rats and our findings, these E(2) effects are probably not sex dependent.
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ABSTRACT: Although the epileptogenic properties of estrogens have been widely demonstrated in several models and species, the mechanism(s) by which estrogens can acutely change seizure parameters including after discharge and seizure durationremains to be determined. In the present study, we examined the role of NMDA (N-methyl-D-aspartate), non-NMDA andestrogen receptors in estradiol benzoate(EB) effects on kindled seizure parameters. Different groups of fully kindled male rats received either EB (30 μg /Kg); EB plus MK801 (2 mg/Kg, as NMDA antagonist); DNQX (7.5 mg/Kg);tamoxifen (TAM, 0.1 mg/Kg, as non- NMDA antagonist) or intra-amygdala injection of anisomycine (30 mmol/mL, a protein synthesis inhibitor). Kindled seizure parameters including after discharge duration (ADD) and stage 5 duration(S5D) were determined at 0.25 and 3 h post sesame oil (EB solvent) or EB treatment. While pretreatment with either MK801 or DNQX could block the ADD prolongation induced by EB at 0.25 h, they had no effect on S5D prolongation at 3 h. Moreover, application of anisomycine or TAM had no effect on estradiol induced ADD and S5D prolongation. These results indicate that both NMDA and non-NMDA receptors could be involved in EB induced ADD prolongation. The observed short termnon-estrogenic receptor or protein synthesis dependent effects of EB may provide a non-genomic mechanism for the stimulatory effects of the steroid on seizure activity.Iranian journal of pharmaceutical research (IJPR) 01/2014; 13(3):987-993. · 0.51 Impact Factor
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ABSTRACT: Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Generally, a twofold or greater increase in seizure frequency during a particular phase of the menstrual cycle could be considered as catamenial epilepsy. Based on this criteria, recent clinical studies indicate that catamenial epilepsy affects 31-60% of the women with epilepsy. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. However, there is no specific drug available today for catamenial epilepsy, which has not been successfully treated with conventional antiepileptic drugs. Elucidation of the pathophysiology of catamenial epilepsy is a prerequisite to develop specific targeted approaches for treatment or prevention of the disorder. Cyclical changes in the circulating levels of estrogens and progesterone play a central role in the development of catamenial epilepsy. There is emerging evidence that endogenous neurosteroids with anticonvulsant or proconvulsant effects could play a critical role in catamenial epilepsy. It is thought that perimenstrual catamenial epilepsy is associated with the withdrawal of anticonvulsant neurosteroids. Progesterone and other hormonal agents have been shown in limited trials to be moderately effective in catamenial epilepsy, but may cause endocrine side effects. Synthetic neurosteroids, which enhance the tonic GABA-A receptor function, might provide an effective approach for the catamenial epilepsy therapy without producing hormonal side effects.Epilepsy research 05/2009; 85(1):1-30. · 2.48 Impact Factor
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ABSTRACT: This review describes the neuroendocrinological aspects of catamenial epilepsy, a menstrual cycle-related seizure disorder in women with epilepsy. Catamenial epilepsy is a multifaceted neuroendocrine condition in which seizures are clustered around specific points in the menstrual cycle, most often around perimenstrual or periovulatory period. Three types of catamenial seizures (perimenstrual, periovulatory and inadequate luteal) have been identified. The molecular pathophysiology of catamenial epilepsy remains unclear. Cyclical changes in the circulating levels of estrogens and progesterone (P) play a central role in the development of catamenial epilepsy. Endogenous neurosteroids such as allopregnanolone (AP) and allotetrahydrodeoxycorticosterone (THDOC) that modulate seizure susceptibility could play a critical role in catamenial epilepsy. In addition, plasticity in GABA-A receptor subunits could play a role in the enhanced seizure susceptibility in catamenial epilepsy. P-derived neurosteroids such as AP and THDOC potentiate synaptic GABA-A receptor function and also activate extrasynaptic GABA-A receptors in the hippocampus and thus may represent endogenous regulators of catamenial seizure susceptibility. Experimental studies have shown that neurosteroids confer greater seizure protection in animal models of catamenial epilepsy, especially without evident tolerance to their actions during chronic therapy. In the recently completed NIH-sponsored, placebo controlled phase 3 clinical trial, P therapy proved to be beneficial only in women with perimenstrual catamenial epilepsy but not in non-catamenial subjects. Neurosteroid analogs with favorable profile may be useful in the treatment of catamenial epilepsy. This article is part of a Special Issue entitled (Hormones & Neurotrauma).Hormones and Behavior 05/2012; · 4.51 Impact Factor