Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, 20156 Milano, Italy.
Neurosci Lett. 2011 Jun 27;497(3):223-30. doi: 10.1016/j.neulet.2011.02.040. Epub 2011 Feb 26.
CNS injuries such as trauma, stroke, viral infection, febrile seizures, status epilepticus occurring either in infancy or during a lifetime are considered common risk factors for developing epilepsy. Long term CNS inflammation develops rapidly after these events, suggesting that a pro-inflammatory state in the brain might play a role in the development of the epileptic process. This hypothesis is corroborated by two main lines of evidence: (1) the upregulation of pro-inflammatory signals during epileptogenesis in brain areas of seizure onset/generalization; (2) pharmacological targeting of specific pro-inflammatory pathways after status epilepticus or in kindling shows antiepileptogenic effects. The mechanisms by which pro-inflammatory molecules might favor the establishment of chronic neuronal network hyperexcitability involve both rapid, non-transcriptional effects on glutamate and GABA receptors, and transcriptional activation of genes involved in synaptic plasticity. This emerging evidence predicts that pharmacological interventions targeting brain inflammation might provide a key to new antiepileptic drug design.
中枢神经系统损伤，如创伤、中风、病毒感染、热性惊厥、癫痫持续状态，无论是在婴儿期还是一生中发生，都被认为是癫痫发生的常见危险因素。这些事件发生后，中枢神经系统炎症迅速发展，提示大脑中的促炎状态可能在癫痫过程的发展中起作用。这一假设得到了两条主要证据的支持：（1）在癫痫发作起始/泛化的脑区，癫痫发生过程中促炎信号的上调；（2）癫痫持续状态或点燃后，针对特定促炎途径的药物靶向治疗显示出抗癫痫作用。促炎分子可能有利于慢性神经元网络过度兴奋的建立的机制既包括对谷氨酸和 GABA 受体的快速、非转录效应，也包括参与突触可塑性的基因的转录激活。这一新兴证据表明，针对大脑炎症的药物干预可能为新型抗癫痫药物设计提供关键。
