Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease.
Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease.
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小胶质启动和对衰老中的继发性损伤的反应性增强，创伤性中枢神经系统损伤和神经退行性疾病。
DOI：
10.1016/j.neuropharm.2014.10.028
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发表时间：
2015-09
影响因子：
4.7
通讯作者：
Godbout JP
中科院分区：
文献类型：
--
作者：
Norden DM;Muccigrosso MM;Godbout JP
中枢神经系统（CNS）的胶质细胞有助于维持大脑的内稳态，支持有效的神经元功能。小胶质细胞是大脑的先天免疫细胞，介导对病原体和损伤的反应。它们在吞噬清除、测量局部微环境和传播炎症信号中起关键作用。内稳态的中断在神经胶质细胞中引起一系列保守的适应性反应。这种反应涉及生化、生理和形态变化，并与影响突触可塑性、认知和行为的细胞因子和次级介质的产生有关。这种宿主优先级的重组代表了一种有益的反应，这种反应通常是适应性的，但当小胶质细胞的特征受到损害时，可能会变得不适应。例如，小胶质细胞可以在衰老、创伤性脑损伤和神经退行性疾病中产生引发或促炎症的mRNA、蛋白质和形态特征。因此，启动小胶质细胞对继发性和亚阈值挑战表现出夸大的炎症反应。小胶质细胞过度炎症反应的后果包括认知缺陷的发展、突触可塑性受损和神经退行性加速。此外，在这种情况下，调节系统的损伤可能使小胶质细胞对负反馈的抵抗力增强，胶质细胞的重要功能可能受到损害和功能失调。总之，这篇综述的目的是讨论在衰老、创伤性中枢神经系统损伤和神经退行性疾病的背景下，小胶质细胞启动和免疫反应的关键概念。
Glia of the central nervous system (CNS) help to maintain homeostasis in the brain and support efficient neuronal function. Microglia are innate immune cells of the brain that mediate responses to pathogens and injury. They have key roles in phagocytic clearing, surveying the local microenvironment and propagating inflammatory signals. An interruption in homeostasis induces a cascade of conserved adaptive responses in glia. This response involves biochemical, physiological and morphological changes and is associated with the production of cytokines and secondary mediators that influence synaptic plasticity, cognition and behavior. This reorganization of host priorities represents a beneficial response that is normally adaptive but may become maladaptive when the profile of microglia is compromised. For instance, microglia can develop a primed or pro-inflammatory mRNA, protein and morphological profile with aging, traumatic brain injury and neurodegenerative disease. As a result, primed microglia exhibit an exaggerated inflammatory response to secondary and sub-threshold challenges. Consequences of exaggerated inflammatory responses by microglia include the development of cognitive deficits, impaired synaptic plasticity and accelerated neurodegeneration. Moreover, impairments in regulatory systems in these circumstances may make microglia more resistant to negative feedback and important functions of glia can become compromised and dysfunctional. Overall, the purpose of this review is to discuss key concepts of microglial priming and immune-reactivity in the context of aging, traumatic CNS injury and neurodegenerative disease.
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影响因子：
4.2
作者：
Bachstetter, Adam D.;Morganti, Josh M.;Jernberg, Jennifer;Schlunk, Andrea;Mitchell, Staten H.;Brewster, Kaelin W.;Hudson, Charles E.;Cole, Michael J.;Harrison, Jeffrey K.;Bickford, Paula C.;Gemma, Carmelina
通讯作者：
Gemma, Carmelina
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
7.8
作者：
Damani MR;Zhao L;Fontainhas AM;Amaral J;Fariss RN;Wong WT
通讯作者：
Wong WT
影响因子：
15.1
作者：
Abraham, Jayne;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.