Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microgl
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Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microglia Jiaojiao Wang 1 & Huijiao Pan 1 & Zhenyu Lin 1 & Chunjin Xiong 1 & Chunhua Wei 1 & Huanhuan Li 1 & Fan Tong 1 & Xiaorong Dong 1 Received: 10 June 2020 / Accepted: 17 September 2020 # The Author(s) 2020
Abstract 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. Keywords Radiation-induced brain injury . Hippocampus . Fractalkine . Microglial . CX3CR1 . Inflammatory . Phagocytosis
Introduction The incidence of brain metastases has significantly increased in the past decades with improved systemic treatment [1]. A majority of patients with metastatic brain tumor have to receive radiotherapy, placing them at a high risk for RIBI,
including a progressive, irreversible cognitive decline, which substantially affects the quality of life of the patients. Due to unknown mechanism of RIBI, lack of effective prevention or long-term treatment, it remains an area of active ongoing research. [2].
Jiaojiao Wang and Huijiao Pan contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02138-3) contains supplementary material, which is available to authorized users. * Xiaorong Dong [email protected]
Chunhua Wei [email protected]
Jiaojiao Wang [email protected]
Huanhuan Li [email protected]
Huijiao Pan [email protected] Zhenyu Lin [email protected] Chunjin Xiong [email protected]
Fan Tong [email protected] 1
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wu
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