Gao Feifei,Ma Yanxi,Zhang Jiahao,et al.Transcriptome analysis of radiation-induced brain injury in mice subjected to Flash whole-brain irradiation with electron beams[J].Chinese Journal of Radiological Medicine and Protection,2025,45(6):537-543 |
Transcriptome analysis of radiation-induced brain injury in mice subjected to Flash whole-brain irradiation with electron beams |
Received:September 12, 2024 |
DOI:10.3760/cma.j.cn112271-20240912-00348 |
KeyWords:Ultra-high dose rate(Flash) irradiation Radiation-induced brain injury Fibroblast growth factor Transcriptome sequencing |
FundProject:国家自然科学基金(82272746);甘肃省自然科学基金(23JRRA569);甘肃省首席科学家计划(23ZDKA011);绵阳市JMRH重点科研项目 |
Author Name | Affiliation | E-mail | Gao Feifei | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing 101408, China | | Ma Yanxi | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China | | Zhang Jiahao | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China | | Cheng Wei | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing 101408, China | | Yu Boyi | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China | | Wang Jianxin | Institute of Applied Electronics, Chinese Academy of Engineering Physics, Mianyang 621900, China | | Liu Xianhong | Zhongjiu Flash Medical Technology Co., Ltd, Mianyang 621000, China | | Jin Xiaodong | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing 101408, China | | Chen Weiqiang | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing 101408, China | chenwq7315@impcas.ac.cn | Li Qiang | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing 101408, China | |
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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. |
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