Transcriptome analysis of radiation-induced brain injury in mice subjected to Flash whole-brain irradiation with electron beams
10.3760/cma.j.cn112271-20240912-00348
- VernacularTitle:电子束Flash全脑照射下小鼠放射性脑损伤的转录组学分析
- Author:
Feifei GAO
1
;
Yanxi MA
;
Jiahao ZHANG
;
Wei CHENG
;
Boyi YU
;
Jianxin WANG
;
Xianhong LIU
;
Xiaodong JIN
;
Weiqiang CHEN
;
Qiang LI
Author Information
1. 中国科学院近代物理研究所,兰州 730000
- Publication Type:Journal Article
- Keywords:
Ultra-high dose rate(Flash) irradiation;
Radiation-induced brain injury;
Fibroblast growth factor;
Transcriptome sequencing
- From:
Chinese Journal of Radiological Medicine and Protection
2025;45(6):537-543
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To reveal the differences in the transcriptome maps of brain tissues in mice subjected to Flash irradiation and conventional dose rate irradiation with electron beams and to explain the biological effect and mechanisms of Flash irradiation from multiple perspectives.Methods:Following the principle of grouping based on approximate body weights, 36 female C57BL/6J mice were divided into three groups, i. e., the control, conventional dose rate irradiation (CONV), and Flash irradiation (Flash) groups, with 12 mice in each group. Both the CONV and Flash groups received a single 15 Gy whole-brain irradiation with 9 MeV electron beams. At 3 d post-irradiation, the whole-brain tissue specimens were collected for hematoxylin-eosin (HE) staining to observe pathological changes. At 1, 3, and 10 weeks post-irradiation, the motion function, cognitive ability, depression level, and spatial memory capacity of the mice were assessed using ethology. At 1 and 10 weeks after behavioral experiments, brain tissue samples were collected and snap-frozen in liquid nitrogen for reference-based transcriptome sequencing. Accordingly, the differences in the transcriptome maps of radiation-induced brain injury between CONV and Flash groups were analyzed.Results:The HE staining-based pathological result revealed that compared to the CONV group, the Flash group exhibited reduced glial cell hyperplasia and inflammatory cell infiltration in brain tissues. Ethological research result at 1 week post-irradiation showed that the CONV group manifested a significantly decreased total traveled distance compared to the control and Flash groups ( t = 5.51, 2.38, P < 0.05) and a significantly increased immobility time compared to the control group ( t = 3.60, P < 0.05). Ethological research result at 3 weeks post-irradiation indicated that compared to the CONV group, the Flash group displayed significantly alleviated cognitive impairment ( t = 3.35, P < 0.05) and reduced depression levels ( t = 2.39, P < 0.05). Ethological research result at 10 weeks post-irradiation demonstrated that the CONV group showed the worst cognitive performance, significantly differing from the control group ( t = 4.53, P < 0.05). Transcriptome sequencing result revealed that besides immune-related pathways, the Flash group also exhibited multiple upregulated metabolic pathways and fibroblast growth factor (FGF)-related pathways compared to the CONV group. Conclusions:Compared to conventional dose rate irradiation, Flash irradiation can effectively alleviate radiation-induced brain injury in mice. This effect is associated with various metabolic pathways (including amino acid metabolism) and FGF-related pathways besides immune pathways.