二甲胺四环素和其他抑制小胶质细胞反应性的药物在预防或治疗癫痫方面有前景吗

W. Lasoń, J. Ślusarczyk, M. Regulska, M. Leśkiewicz, A. Basta-Kaim
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摘要

介绍。越来越多的证据表明,神经炎症过程在癫痫的病理机制中起着重要作用。数据显示,癫痫动物模型和癫痫患者脑组织中促炎细胞因子水平和胶质细胞激活增加,这主要支持了这一假设。另一方面,对这一假设的药理学验证的重视程度较低。的目标。本综述的目的是总结目前关于小胶质细胞调节剂和抗炎剂在设计抗癫痫/抗癫痫药物中的潜在用途的知识,其主要作用机制是基于抑制神经炎症。方法。我们回顾了PubMed和MEDLINE数据库,选择了以下主题的出版物:癫痫、神经炎症、小胶质细胞和具有抗癫痫特性的小胶质细胞调节剂。我们搜索了截至2017年4月的数据库,没有日期限制。复习和讨论。在本文中,我们将讨论癫痫发生的新概念,这些概念不仅关注神经元的变化,而且考虑到神经胶质细胞:小胶质细胞和星形胶质细胞的激活作用。神经炎症,主要是通过增加促炎因子如细胞因子或趋化因子的产生,可能在癫痫的发展中发挥重要作用。在不同的癫痫动物模型和患者的临床研究中,调节中枢神经系统胶质细胞活化和炎症状态的药物具有有益的作用。最有希望的化合物似乎是二甲胺四环素,在一些研究中已被证明具有抗癫痫作用。另一方面,一些抗癫痫药物表现出明显的抗炎效力。结论。有许多数据表明,有重大的机会设计新的抗癫痫药物,其主要作用机制是抑制神经炎症过程。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Do minocycline and other suppressors of microglia reactivity have a future in prevention or treatment of epilepsy
Introduction. An increasing body of evidence points to an important role of neuroinflammatory processes in the pathomechanism of epilepsy. This hypothesis is mainly supported by data showing an increase of pro-inflammatory cytokine levels and glia activation in animal models of epilepsy and in brain tissue of epileptic patients. On the other hand, less emphasis has been put on pharmacological verification of this hypothesis. Aim. The aim of this review is to summarize current knowledge on potential usefulness of microglia regulators and anti-inflammatory agents in designing antiepileptic/antiepileptogenic drugs, with the primary mechanism of action based on the inhibition of neuroinflammation. Methods. We reviewed PubMed and MEDLINE databases to select publications in the topic: epilepsy, neuroinflammation, microglia and microglia regulators with antiepileptic properties. We searched the databases up to April 2017 with no date restrictions. Review and Discussion. In the present paper, we will discuss new concepts of epileptogenesis which focus not only on changes in neurons but also take into consideration the role of activation of glial cells: microglia and astrocytes. Neuroinflammation, mainly through increased production of pro-inflammatory factors such as cytokines or chemokines, may play an important role in the development of epilepsy. Drugs regulating glial cells activation and consequently inflammatory status in the central nervous system have beneficial effects in different animal models of epilepsy as well as in clinical study in patients. The most promising compound seems to be minocycline which in some studies has been shown to possess antiepileptogenetic action. On the other hand, some antiepileptic drugs exhibit marked anti-inflammatory potency. Conclusions. There are much data to suggest that there is significant opportunity for designing new antiepileptic drugs whose primary mechanism of action entails the inhibition of neuroinflammatory processes.
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