Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microglia.
Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microglia.
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Fractalkine通过促进小胶质细胞M2极化对放射性脑损伤的神经保护作用
DOI：
10.1007/s12035-020-02138-3
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发表时间：
2021-03
影响因子：
5.1
通讯作者：
Dong X
中科院分区：
文献类型：
--
作者：
Wang J;Pan H;Lin Z;Xiong C;Wei C;Li H;Tong F;Dong X
放射性脑损伤（Radiation-induced brain injury，RIBI）是肿瘤患者接受脑放射治疗后的严重并发症，越来越多的证据表明小胶质细胞活化在其发病机制中起重要作用。Fractalkine（FKN）是负责小胶质细胞生物活性的重要介质。本研究旨在探讨FKN对放射损伤和放射免疫损伤后活化的小胶质细胞的影响及其机制。我们的研究表明，外源性FKN治疗减少了辐射诱导的促炎因子如IL 1-β和TNFα的产生，促进了辐射后小胶质细胞M1表型向M2表型的转化，并部分恢复了辐射小鼠的空间记忆。此外，通过FKN慢病毒上调FKN/CX 3CR 1促进了海马中辐射诱导的小胶质细胞M2转化，并减轻了辐射小鼠的空间记忆损伤。此外，FKN在抑制仅表达于脑内小胶质细胞的CX 3CR 1的表达的同时，对小胶质细胞和小鼠认知能力的调节作用在辐射后消失。总之，FKN可通过与小胶质细胞上的CX 3CR 1结合而使小胶质细胞向M2表型极化来减弱RIBI。我们的研究揭示了FKN/CX 3CR 1在RIBI中的重要作用，提示促进FKN/CX 3CR 1轴可能是RIBI治疗的一个有希望的策略。本文的在线版本（10.1007/s12035-020-02138-3）包含补充材料，可供授权用户使用。
Radiation-induced brain injury (RIBI) is a serious complication in cancer patients receiving brain radiotherapy, and accumulating evidence suggests that microglial activation plays an important role in its pathogenesis. Fractalkine (FKN) is a crucial mediator responsible for the biological activity of microglia. In this study, the effect of FKN on activated microglial after irradiation and RIBI was explored and the underlying mechanisms were investigated. Our study demonstrated treatment with exogenous FKN diminished radiation-induced production of pro-inflammatory factors, such as IL1-β and TNFα, promoted transformation of microglial M1 phenotype to M2 phenotype after irradiation, and partially recovered the spatial memory of irradiated mice. Furthermore, upregulation of FKN/CX3CR1 via FKN lentivirus promoted radiation-induced microglial M2 transformation in the hippocampus and diminished the spatial memory injury of irradiated mice. Furthermore, while inhibiting the expression of CX3CR1, which exclusively expressed on microglia in the brain, the regulatory effect of FKN on microglia and cognitive ability of mice disappeared after radiation. In conclusion, the FKN could attenuate RIBI through the microglia polarization toward M2 phenotype by binding to CX3CR1 on microglia. Our study unveiled an important role of FKN/CX3CR1 in RIBI, indicating that promotion of FKN/CX3CR1 axis could be a promising strategy for the treatment of RIBI. The online version of this article (10.1007/s12035-020-02138-3) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Morganti JM;Riparip LK;Rosi S
通讯作者：
Rosi S
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
影响因子：
6.1
作者：
Hwang, SY;Jung, JS;Han, IO
通讯作者：
Han, IO
DOI：
10.1152/ajpregu.00236.2015
发表时间：
2016-02-01
影响因子：
2.8
作者：
Stromberg, Anna;Olsson, Karl;Gustafsson, Thomas
通讯作者：
Gustafsson, Thomas
辐射引起的脑损伤的分子，细胞和功能效应：综述。
影响因子：
5.6
作者：
Balentova S;Adamkov M
通讯作者：
Adamkov M