Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center Bryan, TX, USA.
Front Cell Neurosci. 2013 Jul 31;7:115. doi: 10.3389/fncel.2013.00115. eCollection 2013.
This article describes the emerging evidence of hormonal influence on epileptogenesis, which is a process whereby a brain becomes progressively epileptic due to an initial precipitating event of diverse origin such as brain injury, stroke, infection, or prolonged seizures. The molecular mechanisms underlying the development of epilepsy are poorly understood. Neuroinflammation and neurodegeneration appear to trigger epileptogenesis. There is an intense search for drugs that truly prevent the development of epilepsy in people at risk. Hormones play an important role in children and adults with epilepsy. Corticosteroids, progesterone, estrogens, and neurosteroids have been shown to affect seizure activity in animal models and in clinical studies. However, the impact of hormones on epileptogenesis has not been investigated widely. There is emerging new evidence that progesterone, neurosteroids, and endogenous hormones may play a role in regulating the epileptogenesis. Corticosterone has excitatory effects and triggers epileptogenesis in animal models. Progesterone has disease-modifying activity in epileptogenic models. The antiepileptogenic effect of progesterone has been attributed to its conversion to neurosteroids, which binds to GABA-A receptors and enhances phasic and tonic inhibition in the brain. Neurosteroids are robust anticonvulsants. There is pilot evidence that neurosteroids may have antiepileptogenic properties. Future studies may generate new insight on the disease-modifying potential of hormonal agents and neurosteroids in epileptogenesis.
本文描述了激素对癫痫发生的影响的新证据，癫痫发生是指由于脑损伤、中风、感染或长时间发作等不同来源的初始诱发事件，大脑逐渐变得癫痫发作的过程。癫痫发生的分子机制尚不清楚。神经炎症和神经退行性变似乎触发了癫痫发生。人们正在积极寻找真正能预防高危人群癫痫发展的药物。激素在癫痫儿童和成人中起着重要作用。皮质类固醇、孕酮、雌激素和神经甾体已被证明可影响动物模型和临床研究中的癫痫发作活动。然而，激素对癫痫发生的影响尚未得到广泛研究。有新的证据表明，孕酮、神经甾体和内源性激素可能在调节癫痫发生中发挥作用。皮质酮在动物模型中有兴奋作用，并引发癫痫发生。孕酮在致痫模型中具有疾病修饰活性。孕酮的抗癫痫作用归因于其转化为神经甾体，神经甾体与 GABA-A 受体结合，增强大脑中的相位和紧张性抑制。神经甾体是强大的抗惊厥药。有初步证据表明神经甾体可能具有抗癫痫发生的特性。未来的研究可能会为激素和神经甾体在癫痫发生中的疾病修饰潜力提供新的见解。
