Ravizza Teresa, Vezzani Annamaria
Department of Neuroscience IRCCS - Mario Negri Institute for Pharmacological Research Milano Italy.
Epilepsia Open. 2018 Jul 16;3(Suppl Suppl 2):133-142. doi: 10.1002/epi4.12242. eCollection 2018 Dec.
Increasing evidence supports a pathogenic role of unabated neuroinflammation in various central nervous system (CNS) diseases, including epilepsy. Neuroinflammation is not a bystander phenomenon of the diseased brain tissue, but it may contribute to neuronal hyperexcitability underlying seizure generation, cell loss, and neurologic comorbidities. Several molecules, which constitute the inflammatory in the epileptogenic area, activate signaling pathways in neurons and glia resulting in pathologic modifications of cell function, which ultimately lead to alterations in synaptic transmission and plasticity. Herein we report the up-to-date experimental and clinical evidence that supports the neuromodulatory role of inflammatory mediators, their related signaling pathways, and involvement in epilepsy. We discuss how these mechanisms can be harnessed to discover and validate targets for novel therapeutics, which may prevent or control pharmacoresistant epilepsies.
越来越多的证据支持持续的神经炎症在包括癫痫在内的各种中枢神经系统（CNS）疾病中起致病作用。神经炎症并非患病脑组织的旁观者现象，而是可能导致癫痫发作、细胞丢失和神经合并症背后的神经元过度兴奋。构成致痫区域炎症反应的几种分子激活神经元和神经胶质细胞中的信号通路，导致细胞功能的病理改变，最终导致突触传递和可塑性的改变。在此，我们报告支持炎症介质的神经调节作用、其相关信号通路以及参与癫痫的最新实验和临床证据。我们讨论了如何利用这些机制来发现和验证新型治疗方法的靶点，这些靶点可能预防或控制药物难治性癫痫。
