Journal
MOLECULAR NEUROBIOLOGY
Volume 58, Issue 3, Pages 1074-1087Publisher
SPRINGER
DOI: 10.1007/s12035-020-02138-3
Keywords
Radiation-induced brain injury; Hippocampus; Fractalkine; Microglial; CX3CR1; Inflammatory; Phagocytosis
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Funding
- National Natural Science Foundation of China [81573090]
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This study revealed that Fractalkine (FKN) can attenuate Radiation-induced brain injury (RIBI) by promoting microglia polarization towards M2 phenotype through binding to CX3CR1, which could potentially be a promising strategy for the treatment of RIBI.
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-beta and TNF alpha, 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.
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