Peiquan Liu, Min Fu, Dong Liu, Tengfei Chao, Jiaxuan Zhang
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引用次数: 0
Abstract
Radiation therapy is a crucial adjunct treatment for head and neck tumors, as well as primary or metastatic brain tumors. Radiation-induced brain injury is one of the most severe complications, postirradiation, in patients with head and neck tumors, and significantly impacts their quality of life. Currently, there are no effective treatments for radiation-induced brain injury, making the study of radiation-induced molecular mechanisms and the identification of early damage biomarkers critical for the early diagnosis and treatment of such injuries. In this study, twelve male C57 mice aged 6-8 weeks were randomly divided into a control group, a 15 Gy irradiation group, and a 30 Gy irradiation group. Mice were exposed to 6 MV X rays. The control group underwent the same anesthesia procedure as the irradiated groups but did not receive radiation. General health and weight changes were monitored and recorded. Four months postirradiation, mice were subjected to intracranial magnetic resonance imaging [T2-weighted imaging (T2WI)], open field test (OFT), novel object recognition (NOR), followed by a collection of brain tissues for immunofluorescence, SA-β-gal staining, and transcriptomic and metabolomic analyses. Compared to the control group, the 15 Gy and 30 Gy irradiated mice showed reduced activity and weight loss. The irradiated mice exhibited impaired recognition memory in the NOR test and decreased body weight, but radiation had no significant effect on weight or performance in the OFT. Electron microscopy reveals significant demyelination of mouse cortex after irradiation, and MRI T2-weighted imaging demonstrated varying degrees of brain atrophy and ventricular enlargement in irradiated mice compared to the control group. Immunofluorescence staining showed a significant increase in astrocytes and microglia activated after irradiation. SA-β-gal staining revealed significant increases in the numbers of β-gal+ cells in irradiated mice compared to those in untreated control mice. Bioinformatics analysis identified enriched pathways primarily related to lipid metabolism and neuroinflammatory responses; associated metabolites and genes were variously upregulated or downregulated. The findings suggest that radiation-induced brain injury involves complex biological processes, with lipid metabolism disorders and neuroinflammation being the predominant pathological changes observed. Further studies on these metabolic pathways and genes could enhance our understanding of the pathogenic mechanisms underlying radiation-induced brain injury and identify potential therapeutic targets.
期刊介绍:
Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology
and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically
ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or
biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with
chemical agents contributing to the understanding of radiation effects.