Dose-Dependent Dual Effects of Gradient Ionizing Radiation on Neurocognition

Ionizing radiation (IR) exerts complex, dose-dependent biphasic effects on the central nervous system (CNS). This review systematically elucidates the mechanisms underlying the impact of high- and low-dose radiation on neurocognitive function. High-dose radiation (HDR) triggers severe DNA damage, oxidative stress, and neuroinflammatory cascades, leading to neuronal dysfunction, suppression of neurogenesis, and failure of neural circuit reorganization, ultimately resulting in persistent cognitive decline. In contrast, low-dose radiation (LDR) exhibits a unique dual nature: within certain thresholds, it can activate endogenous protective pathways-including DNA repair and antioxidant defenses-thereby promoting neural plasticity and network homeostasis and demonstrating adaptive responses and neuroprotective potential. The research paradigm is shifting from the traditional linear no-threshold (LNT) model towards a dynamic homeostasis model. Future research should prioritize the development of neuroprotective strategies during radiotherapy for high-dose exposure, optimize irradiation modalities, and develop novel radioprotective agents to improve patient outcomes. For LDR, it is crucial to delineate its biological effects and explore its potential for intervening in neurodegenerative diseases. This review aims to provide an integrated theoretical framework for understanding the dose-dependent biphasic regulation of radiation on neurocognition and to outline future directions for developing related protective and therapeutic strategies.