Dose-Dependent Dual Effects of Gradient Ionizing Radiation on Neurocognition

Xiaokun Jian; Beier Jiang; Sixu Li; Tianjiao Min; Yingwei Xu; Ruoshui Xu; Lina Liu; Ying He

PMC · DOI:10.3390/ijms27041842·February 14, 2026

Dose-Dependent Dual Effects of Gradient Ionizing Radiation on Neurocognition

Xiaokun Jian, Beier Jiang, Sixu Li, Tianjiao Min, Yingwei Xu, Ruoshui Xu, Lina Liu, Ying He

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TL;DR

This paper reviews how different radiation doses affect brain function, showing harmful effects at high doses and potential benefits at low doses.

Contribution

The paper introduces a new framework explaining radiation's dual effects on the brain and challenges the traditional linear no-threshold model.

Findings

01

High-dose radiation causes cognitive decline through DNA damage and inflammation.

02

Low-dose radiation can activate protective pathways and promote neural plasticity.

03

A shift from the LNT model to a dynamic homeostasis model is needed for understanding radiation effects.

Abstract

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…

Linked entities

Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.

Genes45

Tnf Tgfb1 Trem2 Syp Ctnnb1 Prdx6-ps2 GFAP CA3 Nos2 Syn1 Il10 Ccr2 Akt1 Creb1 H2ax Ptgs2 Ppara Rad51 Cat Rara Ocln Nfe2l2 Nfkb1 Nqo1 Il1b C3 Atm Cd68 Itgax Sod1 Icam1 CA1 Hmox1 App Sod2 Cldn5 Dlg4 COX2 Tjp1 Pik3r1 Grin1 Trp53-ps Bdnf Dlg1 Il6

Proteins24

Species4

Rattus norvegicus(brown rat · species)Rodentia(rodent · order)Homo sapiens(human · species)Mus musculus(house mouse · species)

Chemicals11

BioRender ATP GSH lipid hydrogen ROS cGMP memantine carbon water glutamate

Diseases60

astrocytosis carcinogenic death demyelination neurological damage brain injury brain damage neurocognitive disorders skull-base tumors ALL neurovascular injury cytotoxic vascular injury cerebrovascular diseases intellectual delay acute radiation syndrome neuronal damage EAE breast cancer depression executive dysfunction dementia amyloid-related deficits multiple sclerosis deterioration of synaptic dysfunction impaired myelination disability tissue injury Cognitive Impairment deficits in associative memory formation brain tumors HDR Inflammatory glial dysfunction Neurodegenerative Diseases injury malignant glioma and prefrontal dysfunction mitochondrial dysfunction PD neurotoxic neural damage behavioral abnormalities neurocognitive failure AD neurogenesis cancer behavioral deficits impairment of BBB traumatic brain injury neuroinflammation CNS damage intelligence white matter injury autoimmune disease DNA Damage deficits in memory, learning, and executive function HSP neurobehavioral abnormalities

Mutations1

P301S

Figures3

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Taxonomy

TopicsEffects of Radiation Exposure · Radiation Therapy and Dosimetry · Brain Metastases and Treatment