| Cui Liang,Lu Xingyu,Shang Hang,et al.A longitudinal evaluation of long-term cognitive behavior and survival performance of mice after FLASH X-ray chest irradiation[J].Chinese Journal of Radiological Medicine and Protection,2026,46(2):183-191 |
| A longitudinal evaluation of long-term cognitive behavior and survival performance of mice after FLASH X-ray chest irradiation |
| Received:July 07, 2025 |
| DOI：10.3760/cma.j.cn112271-20250707-00227 |
| KeyWords:X-rays FLASH irradiation Radiation-induced abscopal effect (RIAE) Behavioral protection Long-term effect |
| FundProject:国家自然科学基金(82272131) |
| Author Name | Affiliation | E-mail | | Cui Liang | School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China | | | Lu Xingyu | School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China | | | Shang Hang | School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China | | | Huang Weirui | School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China | | | Zhou Linghong | School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China | smart@smu.edu.cn |
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| Abstract:: |
| Objective To investigate the effects of ultra-high dose rate (FLASH) chest irradiation with kilovoltage (kV) X-rays on the long-term behavioral performance of mice post-irradiation and to compare the temporal behavioral characteristics between the FLASH and conventional dose rate (CONV) irradiation. Methods Five-week-old female BALB/c mice were selected and, using the random number table method, they were randomly divided into three groups: a FLASH group (mean dose rate: 80 Gy/s), a CONV group (0.2 Gy/s), and a SHAM group. Mice in all groups received chest irradiation at a dose of 20 Gy. The behavioral assessment was performed at 4, 8, and 12 months post-irradiation using the Y-maze test, open field test, novel object recognition test, and nest building test. Results Survival analysis reveals a significantly lower 12-month post-irradiation survival rate in the CONV group than that in the SHAM group (χ2= 6.22, P<0.05). Longitudinal behavior assessment result indicate that in the open field test, mice in the FLASH group maintained higher spontaneous exploration levels than those in the CONV group. Specifically, at 4 months post-irradiation, mice in the FLASH group spent significantly more time exploring the center than those in the CONV group (t=4.29, P<0.01). In contrast, at 12 months post-irradiation, mice in the FLASH group spent significantly less time in the peripheral zones than those in the CONV group (t=4.86, P<0.01). The Y-maze test result indicate that mice in the FLASH group showed higher spatial memory ability than those in the CONV group, as evinced by significantly higher spontaneous alternation rates (t=3.31, P<0.01) and significantly shorter latency to first-arm entry (t=2.70, P<0.05) of the FLASH group compared to the CONV group at 4 months post-irradiation. The novel object recognition test demonstrates that mice in the FLASH group showed both early post-irradiation improvement in recognition ability and long-term functional preservation, with behavioral performance closer to the natural aging process. At 4 months post-irradiation, mice in the FLASH group displayed significantly higher recognition and discrimination indices than those of the CONV group (t=3.87, 4.09, P<0.01). The nest building test result indicate that mice in the FLASH group received significantly higher 48 h nest building scores than those in the CONV group at 12 months post-irradiation (t=5.01, P<0.01). This finding demonstrates that the FLASH group maintained a more intact nest building ability after irradiation. Conclusions During the 12-month observation period, FLASH X-ray irradiation offered significant advantages in multiple dimensions, including survival rate, stress-related behavior, and exploratory behavior, effectively alleviating the chest irradiation-induced functional decline in long-term behavior. In contrast, despite exhibiting age-dependent dynamic changes in some behavioral indicators, the CONV irradiation induced reductions in exploratory behavior and survival rate, as well as impaired instinctive behavior. |
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