Rational modulation of the innate immune system for neuroprotection in ischemic stroke.
Rational modulation of the innate immune system for neuroprotection in ischemic stroke.
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DOI：
10.3389/fnins.2015.00147
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发表时间：
2015
影响因子：
4.3
通讯作者：
Bagetta G
中科院分区：
文献类型：
--
作者：
Amantea D;Micieli G;Tassorelli C;Cuartero MI;Ballesteros I;Certo M;Moro MA;Lizasoain I;Bagetta G
先天免疫系统在缺血性脑损伤的演变中起着双重作用，也参与了不同条件性刺激所产生的缺血耐受。缺血早期，血管周围星形胶质细胞释放细胞因子并激活金属蛋白酶(MMPs)，导致血脑屏障(BBB)破坏和血管源性水肿；而在晚期，它们提供细胞外谷氨酸摄取、BBB再生和神经营养因子释放。同样，小胶质细胞的早期激活通过产生炎性细胞因子，包括肿瘤坏死因子(TNF)和白介素1(IL)-1，活性氧、氮物种和蛋白酶，从而导致缺血性脑损伤。尽管如此，小胶质细胞还通过释放IL-10和肿瘤生长因子β，以及通过吞噬细胞活性和产生生长因子参与晚期修复过程，从而有助于炎症的消退。事实上，缺血后，小胶质细胞/巨噬细胞分化为几种表型：典型的M1促炎表型通过Toll样受体或干扰素-γ激活，而M2表型则由调节介质如IL4、10、13或转化生长因子-β等交替激活。因此，免疫细胞在缺血性脑损伤的演变中发挥着双重作用，因为经典的表型促进损伤，而交替激活的M2巨噬细胞或中性粒细胞促进组织重建和修复。此外，免疫系统的激活减弱参与了缺血耐受，因为不同的预适应刺激通过调节炎症介质发挥作用，包括Toll样受体和细胞因子信号通路。这进一步强调，治疗缺血性中风的免疫调节方法应旨在阻断不利影响，同时促进免疫反应的有益反应。
The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
4.1
作者：
Amantea, D.;Tassorelli, C.;Bagetta, G.
通讯作者：
Bagetta, G.
影响因子：
6.3
作者：
Brea, David;Blanco, Miguel;Castillo, Jose
通讯作者：
Castillo, Jose
影响因子：
3.3
作者：
Amantea, D.;Corasaniti, M. T.;Bagetta, G.
通讯作者：
Bagetta, G.
影响因子：
158.5
作者：
Berkhemer, O. A.;Fransen, P. S. S.;Dippel, D. W. J.
通讯作者：
Dippel, D. W. J.