Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders
Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders
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DOI：
10.1016/j.bcp.2015.11.003
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发表时间：
2016-03-01
影响因子：
5.8
通讯作者：
Suk, Kyoungho
中科院分区：
文献类型：
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作者：
Jha, Mithilesh Kumar;Lee, Won-Ha;Suk, Kyoungho
最近的神经科学研究已经确定成年人的大脑是一个动态器官，具有独特的能力，随着时间的推移而发生变化。神经胶质细胞，特别是小胶质细胞和星形胶质细胞，为大脑提供动力。这些神经胶质细胞的活化是脑损伤和神经变性的神经炎症反应的主要组成部分。神经胶质细胞执行功能反应程序，以响应神经病理学状况所表现的各种微环境信号。活化的小胶质细胞沿着两种功能性极化状态的连续体存在，即M1型（经典/促炎性活化）和M2型（替代/抗炎性活化），如在巨噬细胞中。经典和交替活化的小胶质细胞表型之间的平衡影响CNS中的疾病进展。小胶质细胞的经典激活状态驱动神经炎症反应并介导对神经元的有害影响，而在其替代激活状态（这显然是有益的激活状态）中，小胶质细胞在组织维护和修复中起关键作用。同样，在免疫或炎症微环境的反应中，星形胶质细胞也采用神经毒性或神经保护表型。反应性星形胶质细胞表现出由促炎或抗炎基因表达谱定义的两种不同的功能表型。在这篇综述中，我们已经彻底涵盖了最近的进展，在了解脑和外周胶质细胞的功能极化及其在神经炎症和神经系统疾病的影响。神经胶质细胞对特异性损伤或损伤的反应所采用的可识别表型可以作为神经炎性疾病的有希望的诊断标志物。此外，利用极化胶质细胞的有益作用无疑可以为制定针对各种神经系统疾病的新型胶质治疗策略铺平道路。(C)2015 Elsevier Inc. All rights reserved.
Recent neuroscience research has established the adult brain as a dynamic organ having a unique ability to undergo changes with time. Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain. Activation of these glial cells is a major component of the neuroinflammatory responses underlying brain injury and neurodegeneration. Glial cells execute functional reaction programs in response to diverse microenvironmental signals manifested by neuropathological conditions. Activated microglia exist along a continuum of two functional states of polarization namely M1-type (classical/proinflammatory activation) and M2-type (alternative/anti-inflammatory activation) as in macrophages. The balance between classically and alternatively activated microglial phenotypes influences disease progression in the CNS. The classically activated state of microglia drives the neuroinflammatory response and mediates the detrimental effects on neurons, whereas in their alternative activation state, which is apparently a beneficial activation state, the microglia play a crucial role in tissue maintenance and repair. Likewise, in response to immune or inflammatory microenvironments astrocytes also adopt neurotoxic or neuroprotective phenotypes. Reactive astrocytes exhibit two distinctive functional phenotypes defined by pro- or anti-inflammatory gene expression profile. In this review, we have thoroughly covered recent advances in the understanding of the functional polarization of brain and peripheral glia and its implications in neuroinflammation and neurological disorders. The identifiable phenotypes adopted by neuroglia in response to specific insult or injury can be exploited as promising diagnostic markers of neuroinflammatory diseases. Furthermore, harnessing the beneficial effects of the polarized glia could undoubtedly pave the way for the formulation of novel glia-based therapeutic strategies for diverse neurological disorders. (C) 2015 Elsevier Inc. All rights reserved.