Experimental study in the evaluation of radiation-induced cognitive dysfunction in rats via ¹⁸F-FDG micro-PET metabolic imaging

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. (authors)