Ji Jianfeng,Liu Yunying,Kong Yue,et al.Experimental study in the evaluation of radiation-induced cognitive dysfunction in rats via 18F-FDG micro-PET metabolic imaging[J].Chinese Journal of Radiological Medicine and Protection,2020,40(9):653-658
Experimental study in the evaluation of radiation-induced cognitive dysfunction in rats via 18F-FDG micro-PET metabolic imaging
Received:February 21, 2020  
DOI:10.3760/cma.j.issn.0254-5098.2020.09.001
KeyWords:18F-FDG micro-PET  Whole-brain irradiation  Cognitive dysfunction  Hippocampus  c-Fos
FundProject:国家自然科学基金(81602672);浙江省医药卫生科研项目(2019324448,2019327308)
Author NameAffiliationE-mail
Ji Jianfeng Department of Nuclear Medicine, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, China  
Liu Yunying Department of Pathology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, China  
Kong Yue Department of Radiation Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, China  
Gu Qing Department of Radiation Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, China guqing@zjcc.org.cn 
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Abstract::
      Objective To investigate the correlation between glucose metabolism and neuron activity in radiation-induced brain injury of rat, and to explore the potential implication of 18F-FDG micro-PET in the assessment of radiation-induced cognitive dysfunction. Methods Three-week-old male Sprague-Dawley (SD) rats were divided into two groups, whole-brain irradiation (WBI) group and non-irradiation control group, according to the random number table method. The WBI group was irradiated with 10 Gy X-rays using a small animal precise radiotherapy apparatus. Morris water maze (MWM) test was performed to evaluate the cognitive capability of rats. 18F-FDG micro-PET covering the whole brain was conducted and the micro-PET images were processed by SPM software. The expression of neuronal activity marker c-Fos protein in rat brain was detected by immunohistochemical staining. The neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were detected by immunofluorescence staining. Results Three months after irradiation, MWM place navigation test showed that the latency of whole-brain irradiated rats was longer than that of the control group (t=2.179, 3.393, 3.219, P<0.05). In MWM spatial probe test, the percentage of target quadrant exploring time was reduced in the WBI group compared with the control group (t=3.857, P<0.01). These result suggested that WBI caused hippocampus injury-related cognitive decline. SPM analysis of micro-PET images showed that, after WBI, the glucose metabolism in the hippocampus was significantly reduced (t=5.12, P<0.05), the neuronal active marker c-Fos protein expression was significantly downregulated (t=14.22, P<0.01), and the neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were both decreased (t=18.77, 9.304, P<0.01). Conclusions Glucose metabolism in the hippocampus was reduced after WBI, in consistent with the decrease of neuron activity and the reduction of neurogenesis in this area, suggesting that 18F-FDG micro-PET could be an effective method for assessing radiation-induced cognitive dysfunction.
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