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Objective:To evaluate the effects of whole brain irradiation (WBI) and fecal microbiota transplantation (FMT) on hippocampal neurogenesis and the composition of gut microbiota in mice.Methods:Forty specific pathogen free ICR male mice (8-week-old, weighed 30 g) were divided into four groups by simple random sample method: control group (group C), radiation group (group R), group C+FMT and group R+FMT, 10 in each group. Animal models were established by WBI at a dose of 10 Gy by 4 MeV electron beam. In group C+FMT and group R+FMT, mice were gavaged with normal fecal bacteria suspension on day 2 post-irradiation, while those in group C and group R were gavaged with phosphate buffered saline as alternative. Hippocampal tissues and feces in four groups were collected on day 15 post-irradiation. 16S rRNA sequencing was used to detect the species and abundance of fecal flora. BrdU +/NeuN + immunofluorescence staining was performed to observe the neurogenesis in hippocampus of mice. Results:WBI and FMT had no effect on survival rate and body weight of mice. WBI induced the inhibition of hippocampal neurogenesis and flora disorder. The quantity of Bacteroideae and Rumen bacteria was increased by 28.6% and 102.9%, whereas that of Lactobacillus was significantly decreased by 70.6% ( P<0.05). FMT regulated the abundance of bacteria. The abundance of Enterobacteriaceae was significantly declined by 65.1% ( P=0.028), while that of Lactobacillus was increased by 58.2% ( P=0.015). FMT also promoted hippocampal neurogenesis to some extent after WBI. Conclusions:This preliminary study demonstrates that FMT alleviates the inhibition of hippocampal neurogenesis and flora disorder induced by WBI in mice. Ionizing radiation directly acting on the whole brain of mice indirectly disturbs the composition of gut microbiota, which in turn affects the degree of hippocampal neurogenesis in the brain of mice. There is a bidirectional interaction between gut microbiota and brain.
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Objective:To observe the changes in hippocampus (CA1) and study the effect of chronic intermittent hypobaric hypoxia (CIHH) preconditioning on the memory and cognitive function of mice exposed to the whole brain irradiation.Methods:A total of 48 C57BL/6 male mice were randomly divided into control group, CIHH group, irradiation group (IR group) and CIHH+ IR group. For IR group, the whole brain of mice were irradiated with 10 Gy of 6 MV X-rays in a single fraction. Pretreatment with CIHH was performed by placing mice in a hypobaric chamber before radiation. The mirrors water maze experiment was performed in the four groups to observe the escape latency, the number of crossing platforms and the target quadrant residence time. Nissl staining was used to observe the changes of neuronal cells in hippocampal CA1 region. Immunofluorescence was used to detect the expression of microtubule-associated protein cells (DCX) in the subgranular zone (SGZ) of hippocampal dentate gyrus (DG) to evaluate neurogenesis.Results:After 30 days of whole brain irradiation, the escape latency of mice prolonged gradually, the frequency of crossing platform decreased ( P< 0.001), and the exploration time in the target quadrant decreased ( P<0.001). X-ray irradiation caused disorder of mice neuronal cells, degeneration and necrosis of neuronal cells, and decrease of DCX expression in CA1 region of mice. Compared with IR group, the CIHH+ IR group had shortened the escape latency, increased the frequency of crossing platform [(2.08±0.26) vs. (0.83±0.24), P<0.001], and also increased the exploration time in the target quadrant [(14.12±0.82)s vs. (7.42±0.73)s, P<0.001]. Pretreatment with CIHH also alleviated the deformation and necrosis of neurons in hippocampus, and increased DCX expression in CA1 region. Conclusions:Pretreatment of mice with CIHH plays a protective role in radiation induced hippocampal injury.
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Aim: The aim was to measure doses of eyes and lenses in the presence and absence of shield during whole brain irradiation (WBI). In addition, the dose calculations accuracy of radiation therapy dose plan treatment planning system (TPS) in dose calculation of the eyes and lenses in WBI was evaluated. Materials and Methods: To measure the eyes and lenses doses during WBI, an inhomogeneous phantom of human head was used. Then, the eyes and lenses doses in the presence and absence of shield were measured by EBT3 film. Results: In single fraction with 200 cGy to reference point, average doses received by the left and right eyes in the absence of shield were 20 ± 1.5 and 22 ± 1.0 cGy, respectively, and for the left and right eyes in the presence of shield were 18 ± 2.2 and 21 ± 2 cGy, respectively. In addition, the average dose received by the left and right lenses in the absence of shield were 19.5 ± 0.5 and 18.5 ± 0.5 cGy, respectively, and for the left and right lenses in the presence of shield were 20.5 ± 1.5 and 19.5 ± 1.5 cGy, respectively. The results showed the TPS compared to the film underestimates doses for the eyes and lenses. Conclusion: The average dose received by the eyes and lenses during WBI were estimated around 9–11% of prescribed dose. According to the results, there is probability of radiation-induced cataractogenesis during WBI. By investigating the effect of shield on the lenses and eyes doses, using shield during WBI is not recommended. In addition, the results showed dose calculation accuracy of the TPS for the estimation of doses received by the eyes and lenses during WBI is not acceptable
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Objective To explore the differences in the hippocampal delineation among different radiologists and to evaluate the impact of the delineating guideline training upon improving the accuracy of target area.Methods In this prospective study,20 patients scheduled to receive whole brain radiation therapy were selected.Before and after the delineating guideline training,three physicians from Department of Radiation Oncology delineated the hippocampal targets three times for each patient.One physician from Department of Imaging Diagnosis delivered the delineating guideline training and delineated the hippocampus of 20 patients as the standard target area.The delineating targets before and after the training were statistically compared among different physicians.Results The conformity indexes with the standard target of three physicians before and after the training were 0.66±0.04 and 0.77±0.02,0.62±0.04 and 0.76± 0.02,0.49±0.05 and 0.74±0.04,respectively.The conformity indexes were all statistically increased after the training (all P＜ 0.05).The inter-observer variability significantly differed among different physicians before and after training (all P＜0.05).The coefficient of variance of hippocampal volume before and after training were 0.16±0.06 and 0.08±0.04 with statistical significance (all P＜0.05).Compared with all targets before training,the consistency of each physician was significantly improved after training (all P＜0.05).Conclusion Hippocampal delineation guideline training can improve the accuracy of delineation.
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Objective This study is to investigate the changes in the NFATc 4/3 signaling pathway in rat hippocampus after whole brain radiation. Methods A total of 120 one?month?old male Sprague?Dawley rats were randomly divided into four groups to receive whole brain radiation using 4?MeV electron beams with doses of 0( control) ,2,10,and 20 Gy,respectively,in a single fraction. At 6 hours,12 hours,1 day,3 days,1 week,and 2 weeks after radiation,Western blot and real?time PCR were used to evaluate the changes in expression levels of CaN, NFATc 4/3, p?NFATc 4/3, and GSK?3β. Results There were no significant changes in the expression of NFATc 4/3 or p?NFATc 4/3 at 6 and 12 hours after whole brain radiation. At 1 day after radiation,compared with the control group,the expression of p?NFATc 4/3 in the radiation groups was significantly increased in a dose?dependent manner ( 2 Gy:P= 0. 014;10 Gy:P=0. 011;20 Gy:P=0. 000 );however, there was no significant difference in the expression of NFATc 4/3 between the radiation group and the control group. The expression of NFATc 4/3 was significantly decreased in the radiation groups than in the control group at day 3 ( 2 Gy:P=0. 040;10 Gy:P=0. 000;20 Gy:P=0. 000),1 week (2 Gy:P=0. 692;10 Gy:P=0. 032;20 Gy:P=0. 021),and 2 weeks (2 Gy:P=0. 001;10 Gy:P=0. 000;20 Gy:P=0. 000) after radiation,while there was no significant difference in the expression of p?NFATc 4/3 between any two groups. There were no time?or dose?dependent changes in expression of CaN or GSK?3β. Conclusions Ionization radiation has an inhibitory effect on the NFATc 4/3 signaling pathway in rat hippocampus. Combined with our previous results,this study suggests that radiation?induced cognitive dysfunction is associated with the NFATc 4/3 signaling pathway.
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Facial palsy as the presenting symptom of leukemia is very rare, especially in acute myeloid leukemia. A review of the medical literature identified reports on 8 children with AML who had facial paralysis as the presenting sign. Whole brain irradiation (WBI) has been applied in most cases. We present the cases of 3 such children. Achieving a remission without WBI, the patients underwent stem cell transplantations (SCTs). Two patients remain event-free 52 months and 62 months after allotransplants. Facial palsy was the harbinger of leukemic relapse in one case after autotransplant. This patient is disease-free 59 months after unrelated SCT rescue. Facial palsy persisted in 2 cases. Allogeneic SCT without WBI may be an effective therapy in patients presenting with facial palsy. A brief review of the literature is presented here.