Abstract: Radiotherapy serves as a primary therapeutic approach for head and neck tumors. However, it subsequently develops radiation⁃induced brain injury and radiation⁃induced cognitive impairment (RICI). RICI is characterized by progressive deficits in  memory, attention, and executive function, yet the underlying mechanisms remain inadequately understood. As the innate immune effector cells of the central nervous system (CNS), the dynamic polarization of microglia is a critical role in the pathological processes of RICI. Accumulating evidence suggests that dysregulation of microglial polarization significantly contributes to the etiology of RICI. Beyond direct neuronal damage, ionizing radiation disrupts immune homeostasis, thereby amplifying secondary injury. During the acute phase of radiotherapy, damaged cells release injury⁃related molecular patterns such as HMGB1, which activate the TLR4/NF⁃κB signaling pathway and the NLRP3 inflammasome. This activation prompts microglia to rapidly polarize into the M1 phenotype (pro⁃inflammatory/damage type), subsequently releasing inflammatory mediators such as IL⁃1β and TNF⁃α. As the disease progresses to the chronic stage, the transformation of microglia from M1 to M2 phenotype (anti⁃inflammatory/repair type) is blocked, leading to persistent chronic neuroinflammation, which in turn compromises hippocampal neurogenesis and synaptic plasticity, ultimately resulting in cognitive dysfunction. This review summarizes the spatiotemporal characteristics of microglial polarization in RICI and elucidates the associated molecular regulatory mechanisms, aims to provide a theoretical basis for the prevention and treatment of radiation⁃induced cognitive impairment. 

Key words: Nervous system tumor, Microglia, Radiation brain injury, Cognitive impairment, Neuroinflammatory response, TLR4/NF?κB signaling pathway, NLRP3 inflammasome