Journal Article

Neuroprotective Effect of Fractalkine on Radiation-induced Brain Injury Through Promoting the M2 Polarization of Microglia

Dong, Xiaorong, Wang, Jiaojiao, Wei, Chunhua, Tong, Fan, Pan, Huijiao, Lin, Zhenyu, Xiong, Chunjin, Li, Huanhuan

2021

Overview

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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Animals / Biological activity / Biomedical and Life Sciences / Biomedicine / Brain Injuries - drug therapy / Brain Injuries - etiology / Brain Injuries - pathology / Brain injury / Cell Biology / Cell Line / Cell Polarity - drug effects / Cesium Radioisotopes / Chemokine CX3CL1 - pharmacology / Chemokine CX3CL1 - therapeutic use / Cognitive ability / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - etiology / Cognitive Dysfunction - pathology / Cranial Irradiation / CX3C Chemokine Receptor 1 - metabolism / CX3CR1 protein / Female / Fractalkine / Genetic transformation / Genotype & phenotype / Hippocampus - pathology / Inflammation / Inflammation Mediators - metabolism / Interleukin 1 / Memory / Mice / Mice, Inbred C57BL / Microglia / Microglia - drug effects / Microglia - metabolism / Microglia - pathology / Neurobiology / Neurogenesis - drug effects / Neurology / Neuroprotection / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / Neurosciences / Phagocytosis - drug effects / Phenotype / Phenotypes / Polarization / Proliferating Cell Nuclear Antigen - metabolism / Radiation Injuries - complications / Radiation Injuries - drug therapy / Radiation Injuries - pathology / Radiation therapy / Spatial Learning / Spatial memory / Spatial Memory - drug effects / Traumatic brain injury / Tumor necrosis factor-α