Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.
Neuropharmacology. 2020 May 1;167:107742. doi: 10.1016/j.neuropharm.2019.107742. Epub 2019 Aug 14.
Neuroinflammation and reactive oxygen and nitrogen species are rapidly induced in the brain after acute cerebral injuries that are associated with an enhanced risk for epilepsy in humans and related animal models. These phenomena reinforce each others and persist during epileptogenesis as well as during chronic spontaneous seizures. Anti-inflammatory and anti-oxidant drugs transiently administered either before, or shortly after the clinical onset of symptomatic epilepsy, similarly block the progression of spontaneous seizures, and may delay their onset. Moreover, neuroprotection and rescue of cognitive deficits are also observed in the treated animals. Therefore, although these treatments do not prevent epilepsy development, they offer clinically relevant disease-modification effects. These therapeutic effects are mediated by targeting molecular signaling pathways such as the IL-1β-IL-1 receptor type 1 and TLR4, P2X7 receptors, the transcriptional anti-oxidant factor Nrf2, while the therapeutic impact of COX-2 inhibition for reducing spontaneous seizures remains controversial. Some anti-inflammatory and anti-oxidant drugs that are endowed of disease modification effects in preclinical models are already in medical use and have a safety profile, therefore, they provide potential re-purposed treatments for improving the disease course and for reducing seizure burden. Markers of neuroinflammation and oxidative stress can be measured in blood or by neuroimaging, therefore they represent testable prognostic and predictive biomarkers for selecting the patient's population at high risk for developing epilepsy therefore eligible for novel treatments. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
神经炎症以及活性氧和氮物种会在急性脑损伤后迅速在大脑中产生，这与人类和相关动物模型中癫痫风险增加有关。这些现象相互加强，并在癫痫发生期间以及慢性自发性癫痫发作期间持续存在。在症状性癫痫发作的临床发作之前或之后不久，短暂给予抗炎和抗氧化药物同样可以阻止自发性癫痫发作的进展，并可能延迟其发作。此外，在治疗动物中还观察到神经保护和认知缺陷的挽救。因此，尽管这些治疗方法不能预防癫痫的发展，但它们提供了具有临床相关性的疾病修饰作用。这些治疗效果是通过靶向分子信号通路来介导的，例如 IL-1β-IL-1 受体类型 1 和 TLR4、P2X7 受体、转录抗氧化因子 Nrf2，而 COX-2 抑制对减少自发性癫痫发作的治疗效果仍存在争议。一些在临床前模型中具有疾病修饰作用的抗炎和抗氧化药物已经在医疗中使用，并且具有安全性，因此，它们为改善疾病进程和减少癫痫发作负担提供了潜在的再利用治疗方法。神经炎症和氧化应激的标志物可以通过血液或神经影像学来测量，因此它们是可测试的预后和预测生物标志物，用于选择具有发展为癫痫高风险的患者人群，从而有资格接受新的治疗方法。本文是题为“21 世纪的新癫痫治疗方法-从抗癫痫药物到癫痫的预防、修饰和治疗”的特刊的一部分。
