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1.
Neuroactive steroids and seizure susceptibility   总被引:4,自引:0,他引:4  
There is increasing clinical and experimental evidence that hormones, in particular sex steroid hormones, influence neuronal excitability and other brain functions. The term 'neuroactive steroids' has been coined for steroids that interact with neurotransmitter receptors. One of the best characterized actions of neuroactive steroids is the allosteric modulation of GABA(A)-receptor function via binding to a putative steroid-binding site. Since neuroactive steroids may interact with a variety of other membrane receptors, excitatory as well as inhibitory, they may have an impact on the excitability of specific brain regions. Neuronal excitability is enhanced by estrogen, whereas progesterone and its metabolites exert anticonvulsant effects. Testosterone and corticosteroids have less consistent effects on seizure susceptibility. Apart from these particular properties, neuroactive steroids may regulate gene expression via progesterone receptors. Based on their molecular properties, these compounds appear to have a promising therapeutical profile for the treatment of different neuropsychiatric diseases including epilepsy. This review focuses on the effects of neuroactive steroids on neuronal excitability and their putative impact on the physiology of epileptic disorders.  相似文献   

2.
Gonadal steroid hormones can markedly affect seizure susceptibility. Ovariohysterectomized female rats given ovarian steroid hormone supplements were used to evaluate the effects of ovarian steroids on epileptiform activity in hippocampal slices in vitro and on flurothyl-induced seizures in vivo. Seizure susceptibility was compared in the entorhinal cortex (EC) and CA1 regions of the hippocampus perfused with Mg(2+)-free medium, which leads to epileptiform discharges caused by a relief of voltage-dependent NMDA receptor block. After in vivo treatment with 500 microg of progesterone for 2 h prior to slice preparation, the latency to onset of low Mg(2+)-induced epileptiform activity of slices was significantly prolonged compared to slices from controls. In contrast, progesterone replacement accelerated the development of epileptiform activity in the CA1 region. Neither estrogen alone (2 x 2 microg of estradiol benzoate, 48 and 24 h prior to the experiment), nor a combined treatment with estrogen plus progesterone, significantly affected seizure susceptibility in either CA1 or the EC. There were no consistent effects of estrogen or progesterone, alone or in combination, on flurothyl-induced seizures in vivo. The data suggest that in vitro, progesterone alters seizure susceptibility in a site- and seizure model-specific fashion. The differential effects of progesterone may be due to differential expression of progesterone receptor isoforms or metabolites in specific brain areas suggesting that selective modulation of NMDA receptor-dependent epileptiform activity may play a role in hormonal effects on epileptogenesis.  相似文献   

3.
Summary: Hormones influence brain function from gestation throughout life and may affect the seizure threshold by altering neuronal excitability. Estrogen enhances and progesterone diminishes neuronal excitability experimentally, whereas testosterone and corticosteroids have less consistent effects. Hormonal effects in the CNS also depend on the region of brain in which the hormone acts. Sites of action for most steroid hormones include the hypothalamus and limbic cortex, providing a mechanism for modulating behavior and endocrine function. Seizure patterns may change at certain life stages, perhaps as a result of alterations in hormones. At puberty, epilepsy and benign rolandic epilepsy often remit, while juvenile myoclonic and photosensitive epilepsy may arise. Other types of epilepsy do not respond predictably to events in the reproductive life or to advancing age. In some women, fluctuations in hormones over the menstrual cycle appear to increase seizure vulnerability, probably reflecting changes in relative amounts of estrogen and progesterone. Seizure patterns can be altered, for better or worse, during pregnancy. Whether this reflects the effects of hormones or changes in levels of antiepileptic drugs is not resolved. More information is needed about changes in established epilepsy at menopause and in the elderly. Better understanding of endocrine effects on seizures over a lifetime should lead to more effective epilepsy therapies.  相似文献   

4.
This review examines the interaction of steroid hormones, glucocorticoids and estrogen, and gp120, a possible causal agent of acquired immune deficiency syndrome-related dementia complex. The first part of the review examines the data and mechanisms by which gp120 may cause neurotoxicity and by which these steroid hormones effect cell death in general. The second part of the review summarizes recent experiments that show how these steroid hormones can modulate the toxic effects of gp120 and glucocorticoids exacerbating toxicity, and estrogen decreasing it. We then examine the limited in vivo and clinical data relating acquired immune deficiency syndrome-related dementia complex and steroid hormones and speculate on the possible clinical significance of these findings with respect to acquired immune deficiency syndrome-related dementia complex.  相似文献   

5.
Hormonal Effects on Epilepsy in Women   总被引:9,自引:2,他引:7  
Summary: Some female gonadal and adrenal steroid hor-mones and their related pituitary peptides have neuroactive effects that can influence seizures. These effects may play a significant role in the pathophysiology of epilepsy, the pattern of seizure occurrence, therapeutic interventions using naturally occurring hormones, and the development of hormone-based neuroactive synthetic analogues with potent antiepileptic properties.  相似文献   

6.
Seizures do not occur randomly in the majority of people with epilepsy. They tend to cluster. Seizure clusters, in turn, commonly occur with a temporal rhythmicity that shows a readily identifiable and predictable periodicity. When the periodicity of seizure exacerbation in women conforms to that of the menstrual cycle, it is commonly known as catamenial epilepsy. This may be attributable to 1) the neuroactive properties of steroid hormones and 2) the cyclic variation in their serum levels. If hormones play a role in seizure occurrence, hormones may also have a role in treatment. Progesterone has potent GABAergic metabolites that may provide safe and effective seizure control in women who have catamenial epilepsy.  相似文献   

7.
The present study examined the ovarian hormonal regulation of seizure susceptibility in prenatally morphine- and saline-exposed adult female rats in the flurothyl seizure model in vivo, and in low-magnesium-induced epileptiform activity in brain slices, in vitro. All females were ovariohysterectomized (OVX); some received either estrogen (E) or progesterone (P) replacement, while others were injected with E+P sequentially. In prenatally saline-treated control females, there was an increase in the flurothyl-induced clonic seizure threshold (anticonvulsant effect) in the presence of both hormones (E+P) compared to OVX controls. In morphine-exposed females, there was an increase in the flurothyl-induced clonic seizure threshold after an E injection alone while there was a reduced tonic–clonic seizure threshold in the presence of both hormones (E+P) compared to the hormone treatment-matched group of saline-exposed females. In control females, in low magnesium medium in vitro, the development of two types of epileptiform activity (seizure-like events and status of short discharges) was not affected by the different hormonal conditions. However, prenatal morphine exposure suppressed the development of both types of epileptiform activity in the E-injected females compared to the E-injected, control females. The present data demonstrate that the anticonvulsant effects of P on seizure susceptibility requires the presence of E. Furthermore, prenatal morphine exposure alters ovarian steroid hormone-regulated seizure susceptibility.  相似文献   

8.
Scharfman HE  MacLusky NJ 《Epilepsia》2006,47(9):1423-1440
It is clear from both clinical observations of women, and research in laboratory animals, that gonadal hormones exert a profound influence on neuronal excitability, seizures, and epilepsy. These studies have led to a focus on two of the primary ovarian steroid hormones, estrogen and progesterone, to clarify how gonadal hormones influence seizures in women with epilepsy. The prevailing view is that estrogen is proconvulsant, whereas progesterone is anticonvulsant. However, estrogen and progesterone may not be the only reproductive hormones to consider in evaluating excitability, seizures, or epilepsy in the female. It seems unlikely that estrogen and progesterone would exert single, uniform actions given our current understanding of their complex pharmacological and physiological relationships. Their modulatory effects are likely to depend on endocrine state, relative concentration, metabolism, and many other factors. Despite the challenges these issues raise to future research, some recent advances have helped clarify past confusion in the literature. In addition, testable hypotheses have developed for complex clinical problems such as "catamenial epilepsy." Clinical and animal research, designed with the relevant endocrinological and neurobiological issues in mind, will help advance this field in the future.  相似文献   

9.
Hormonal considerations in women with seizures   总被引:1,自引:0,他引:1  
The relationships between seizures in epileptic women and the hormones estrogen and progesterone are under increasing study. Serum concentrations of estrogen and progesterone parallel cerebrospinal concentrations, and circulating sex hormones are concentrated in specific areas of the brain that regulate sexual behavior. These centers include two potentially epileptogenic regions--the amygdala and hippocampus. Many of these structures are physiologically affected in vitro by estrogen and progesterone. Exogenous sex hormones change the seizure threshold in animal models of epilepsy. Cyclical hormonal variations may influence electroencephalographic activity and affect seizure frequency in women with epilepsy. Hormonal therapy may be appropriate adjunctive anticonvulsant treatment, particularly for women with seizures that are catamenial or associated with a menstrual or reproductive endocrine disorder.  相似文献   

10.
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