Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province 430022, China.
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province 430022, China.
Neurobiol Dis. 2023 Sep;185:106249. doi: 10.1016/j.nbd.2023.106249. Epub 2023 Aug 1.
Epilepsy is one of most common chronic neurological disorders, and the antiseizure medications developed by targeting neurocentric mechanisms have not effectively reduced the proportion of patients with drug-resistant epilepsy. Further exploration of the cellular or molecular mechanism of epilepsy is expected to provide new options for treatment. Recently, more and more researches focus on brain network components other than neurons, among which microglia have attracted much attention for their diverse biological functions. As the resident immune cells of the central nervous system, microglia have highly plastic transcription, morphology and functional characteristics, which can change dynamically in a context-dependent manner during the progression of epilepsy. In the pathogenesis of epilepsy, highly reactive microglia interact with other components in the epileptogenic network by performing crucial functions such as secretion of soluble factors and phagocytosis, thus continuously reshaping the landscape of the epileptic brain microenvironment. Indeed, microglia appear to be both pro-epileptic and anti-epileptic under the different spatiotemporal contexts of disease, rendering interventions targeting microglia biologically complex and challenging. This comprehensive review critically summarizes the pathophysiological role of microglia in epileptic brain homeostasis alterations and explores potential therapeutic or modulatory targets for epilepsy targeting microglia.
癫痫是最常见的慢性神经障碍之一,针对神经中心机制开发的抗癫痫药物并没有有效地降低耐药性癫痫患者的比例。进一步探索癫痫的细胞或分子机制有望为治疗提供新的选择。最近,越来越多的研究关注神经元以外的脑网络成分,其中小胶质细胞因其多样的生物学功能而引起了广泛关注。作为中枢神经系统的固有免疫细胞,小胶质细胞具有高度可塑性的转录、形态和功能特征,在癫痫进展过程中可以以依赖于上下文的方式动态变化。在癫痫的发病机制中,高反应性小胶质细胞通过分泌可溶性因子和吞噬作用等关键功能与致痫网络中的其他成分相互作用,从而不断重塑癫痫脑微环境的景观。事实上,小胶质细胞在疾病的不同时空背景下似乎既有致痫作用,也有抗痫作用,这使得针对小胶质细胞的干预措施在生物学上变得复杂而具有挑战性。本综述批判性地总结了小胶质细胞在癫痫脑内稳态改变中的病理生理作用,并探讨了针对小胶质细胞的癫痫治疗的潜在治疗或调节靶点。