Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via Giuseppe La Masa 19, 20156 Milan, Italy.
Nat Rev Neurol. 2011 Jan;7(1):31-40. doi: 10.1038/nrneurol.2010.178. Epub 2010 Dec 7.
Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.
癫痫是第三大常见的慢性脑部疾病,其特征是存在持久的发作倾向。尽管在癫痫的药物治疗和手术治疗方面取得了进展,但对于导致个体发作的过程以及使健康大脑变得癫痫的机制,我们知之甚少。这些知识上的差距阻碍了更好的预防治疗和治愈方法的发展,因为大约 30%的癫痫病例对目前的治疗方法有抗药性。在这里,我们重点介绍越来越多的证据,这些证据支持炎症介质(由脑细胞和外周免疫细胞释放)在个体发作和致痫过程中的参与。我们首先描述了大脑炎症和免疫的各个方面,然后探讨了临床和实验研究中炎症与癫痫之间关系的证据。随后,我们讨论了癫痫发作如何引起炎症,以及这种炎症是否反过来影响癫痫发作的发生和严重程度以及与癫痫发作相关的神经元死亡。进一步深入了解炎症在癫痫发作和恶化中的复杂作用,应该为抗癫痫药物的设计提供新的分子靶点,这些药物不仅可以抑制这种疾病的症状,还可以预防或消除疾病的发病机制。