Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Inflamm Res. 2023 Apr;72(4):683-701. doi: 10.1007/s00011-023-01700-8. Epub 2023 Feb 6.
Epilepsy is a group of chronic neurological disorders that have diverse etiologies but are commonly characterized by spontaneous seizures and behavioral comorbidities. Although the mechanisms underlying the epileptic seizures mostly remain poorly understood and the causes often can be idiopathic, a considerable portion of cases are known as acquired epilepsy. This form of epilepsy is typically associated with prior neurological insults, which lead to the initiation and progression of epileptogenesis, eventually resulting in unprovoked seizures. A convergence of evidence in the past two decades suggests that inflammation within the brain may be a major contributing factor to acquired epileptogenesis. As evidenced in mounting preclinical and human studies, neuroinflammatory processes, such as activation and proliferation of microglia and astrocytes, elevated production of pro-inflammatory cytokines and chemokines, blood-brain barrier breakdown, and upregulation of inflammatory signaling pathways, are commonly observed after seizure-precipitating events. An increased knowledge of these neuroinflammatory processes in the epileptic brain has led to a growing list of inflammatory mediators that can be leveraged as potential targets for new therapies of epilepsy and/or biomarkers that may provide valued information for the diagnosis and prognosis of the otherwise unpredictable seizures. In this review, we mainly focus on the most recent progress in understanding the roles of these inflammatory molecules in acquired epilepsy and highlight the emerging evidence supporting their candidacy as novel molecular targets for new pharmacotherapies of acquired epilepsy and the associated behavioral deficits.
癫痫是一组慢性神经系统疾病，病因多样，但通常以自发性癫痫发作和行为合并症为特征。尽管癫痫发作的机制大多仍不清楚，且病因通常是特发性的，但相当一部分病例被称为获得性癫痫。这种形式的癫痫通常与先前的神经损伤有关，这些损伤导致癫痫发生的启动和进展，最终导致无诱因的癫痫发作。过去二十年的大量证据表明，大脑内的炎症可能是获得性癫痫发生的一个主要因素。正如越来越多的临床前和人体研究证据表明，神经炎症过程，如小胶质细胞和星形胶质细胞的激活和增殖、促炎细胞因子和趋化因子的产生增加、血脑屏障破坏以及炎症信号通路的上调，在诱发癫痫发作的事件后通常会观察到。对癫痫大脑中这些神经炎症过程的认识不断增加，导致了越来越多的炎症介质被认为是癫痫新疗法的潜在靶点，以及可能为不可预测的癫痫发作的诊断和预后提供有价值信息的生物标志物。在这篇综述中，我们主要关注最近在理解这些炎症分子在获得性癫痫中的作用方面的进展，并强调支持它们作为获得性癫痫和相关行为缺陷的新型药物靶点候选物的新兴证据。
