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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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In addition to induce cell death in tumor cells, ionizing radiation (IR) regulates many biological behaviors of malignant tumors, such as intrinsic radiosensitivity, invasion and metastasis, angiogenesis, as well as immune response of tumor cells. The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 are highly expressed in a variety of malignant tumors, and are involved in the process of remote metastasis, blood vessel formation, immune regulation, and therapeutic resistance of malignant tumors. Recent studies have found that the CXCL12/CXCR4 signal axis plays critical roles in the IR-regulated biological behavior of malignant tumors. This paper reviews the roles of CXCL12/CXCR4 signal axis in the biological behavior changes of irradiated malignant tumors.
ABSTRACT
In addition to induce cell death in tumor cells,ionizing radiation (IR) regulates many biological behaviors of malignant tumors,such as intrinsic radiosensitivity,invasion and metastasis,angiogenesis,as well as immune response of tumor cells.The C-X-C motif chemokine ligand 12 (CXCL12) and its receptor CXCR4 are highly expressed in a variety of malignant tumors,and are involved in the process of remote metastasis,blood vessel formation,immune regulation,and therapeutic resistance of malignant tumors.Recent studies have found that the CXCL12/CXCR4 signal axis plays critical roles in the IR-regulated biological behavior of malignant tumors.This paper reviews the roles of CXCL12/CXCR4 signal axis in the biological behavior changes of irradiated malignant tumors.
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To investigate the effect of ultrasound-guided percutaneous injection of cinobufotalin or anhydrous ethanol in the treatment of portal vein tumor thrombus (PVTT) through a comparative analysis. MethodsA total of 56 patients with PVTT after liver cancer surgery, who were admitted to the 94th Hospital of PLA from October 2009 to December 2011, were enrolled. Among these patients, 27 underwent ultrasound-guided percutaneous injection of cinobufotalin (cinobufotalin group) and 29 underwent ultrasound-guided percutaneous injection of anhydrous ethanol (anhydrous ethanol group). The clinical outcome and survival time were compared between the two groups after treatment, and the levels of total bilirubin (TBil), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) before and after treatment were compared. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, the rank sum test was used for comparison of ranked data, and the Kaplan-Meier method was used for survival analysis. ResultsThe response rate showed no significant difference between the cinobufotalin group and the anhydrous ethanol group (63.0% vs 58.6%, χ2=0.111, P＞0.05). After treatment, the cinobufotalin group had significantly lower levels of TBil, ALT, and AST than the anhydrous ethanol group (t=2.24, 2.40, and 2.39, all P＜0.05). The 6-month, 1-year, and 2-year survival rates showed no significant differences between the cinobufotalin group and the anhydrous ethanol group (81.5%/63.0%/29.6% vs 82.8%/586%/31.0%, χ2=0.016, 0.111, and 0.013, all P＞0.05). ConclusionUltrasound-guided percutaneous injection of cinobufagin or anhydrous ethanol has similar short- and long-term effects in the treatment of PVTT and can inhibit the growth of tumor thrombus and prolong survival time, but cinobufagin is superior to anhydrous ethanol in the aspect of protecting liver function.
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Objective To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group ( C ) , swimming group ( C-S ) , radiation group( R) , and radiation plus swimming group( R-S) . Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P0?05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation ( P < 0?05 ) , but this reduction was attenuated by the chronic forced swimming stress. Conclusion The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus.
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ObjectiveTo investigate the relationship between 10 cGy whole brain radiation and cognitive dystunction.MethodsThirty-two male Sprague-Dawley rats at age one month were randomized into irradiation and sham exposed groups.Behavioral and histopathological tests were performed 3 months after irradiation in the order of open field,Morris water maze,passive avoidance,and histopathological test.Comparison between the two groups was conducted using independent samples t-test.ResultsIn the place navigation test of Morris water maze,irradiation group showed significantly longer latency than sham exposed group on day 3 and 4 ( t =2.91 and 2.65,all P ＜ 0.05 ).In the total latency of the place navigation,irradiation group also presented longer latency comparing with sham exposed group ( t =2.63,P ＜ 0.05 ).In the spatial probe test of Morris water maze,the open field test and the passive avoidance test showed no significant difference between the two groups ( t =0.92,0.59,0.83,all P ＞ 0.05 ).The histopathological examination had no significant difference either.ConclusionWhole brain radiation of 10 cGy could partly injury the cognitive function of the rat.