The Preliminary Study Of Glucocorticoids Protective Effect On Radiation Induced Hippocampus Injury

Objective Radiation therapy is the most effective means to treat with malignant tumors.However, it also can bring cognitive dysfunction, which have characterizd of memory loss. The hippocampus plays an important role in human advanced functions such as emotional integration learning and memory ability.And radiation induced hippocampus injury has become an increasingly important topic concerned. Radiation therapy induced brain injury involves the inflammatory response.So the means of preventing and treating of radiation encephalopathy has become a research focus. Glucocorticoids have been widely used in clinical, yet the mechanisms of Glucocorticoids how to prevent and treat radiation induced-brain injury has not fully understand, our experiment aim to preliminarily explore the mechanisms of Glucocorticoids in the radiation induced-brain injury throughing establish the model of low-dose fractioned brain irradiation.And to provide a theoretical basis on the prevention and treatment of radiation encephalopathy in clinical.Methods48kunming mice randomly divided into the control group、the control group+DXM in intervention group、30Gy model group、model group+DXM in treatment group. each group12.In the awake state, the mice was placed on the linear accelerator platform under the lead mode, which has many holes insides.The beam thronghing the holes can precisely position on the brain. With the help of the self-made mold, which is comtribute to fixed the irradiation brain.2Gy/day,5times/week, under continuous exposure in three weeks, the cumulative dose is30Gy.After radiation, the control group+DXM in intervention group and model+DXM in treatment group were given respectively DXM1mg/KG in intreperitioneal injection. The ability of spatial learning and memory was tested by Morris Water Maze respectively before irradiation and after3weeks DXM treatment with mice.Each group randomly selected6mices,through the number of astrocytes(GFAP+) positive cells with the method of immunohistochemistry before treatment and post DXM treatment, to evaluate the differentiation of the neural stem cells(NSCs)and the response of glial cells in the central nervous system(CNS) before and post DXM treatment. We are aim to detect the number of tumor necrosis factor-a(TNF-a) positive cells by the method of immunohistochemistry,further to evaluate the level of the neuroinflammation in CNS before and post DXM treatment. And make the pathologic slices such as Nissl staining and HE staining. At the same time, each group were randomly selected6mices, which were injected with Evans Blue(EB)by tail vein. Through measure the change of water content and EB content in the brain before and after DXM treatment, we aim to evaluate the change of the blood-brain barrier(BBB) before and post DXM treatment.Results1.General situation:The model group and model+DXM treatment group appear the psychiatric symptoms such as irritability、biting each other after the irradiation.The model group can be seen the sign of comet tail (attached figure).The model group and model+DXM treatment group appear the mild hair lightly after3weeks radiation,yet the symptoms eased by treating with DXM in model+DXM treatment group.No significant difference in body weight in each group before irradiation, The model group and model+DXM treatment group compared with the control group have significant difference after3weeks radiation.The body weight in the model+DXM treatment group rebeck to the level of the control group after2weeks DXM treatment.Although the model group appear to recome,there is no significant difference compared with the control group. The body weight in the control group and the control+DXM in treatment group have increased gradually, and have no significant difference.2.Behavior test:Before radiation6weeks, although the number of acrossing the platform and the first time of throughing the platform have no appearly difference in the control group,the active time have increased significantly in first quadrant and central ring.However,after the DXM treatment the above difference rebeck to the level of the control group. Not only the number of times of throughing the platform decreased significantly (P<0.01),the first time of finding the platform also prolong significantly(P<0.01)in the model group after radiation6weeks. However, the number of throughing the platform、the first time of acrossing the platform and the time of finding the platform in each quadrant or ring have not significant differences after DXM treatment.The control+DXM treatment group and the model+DXM treatment group have no significant difference in behavior test.3.Nissl staining:Compared with the control group,model group is statistically decreased(P<0.01)in the hippocampal CA1,and the model+DXM in treatment group compared with model group is increased statistically (P<0.05) in the hippocampal CA3after radiation therapy. The control group+DXM in intervention roup compared with the control group is decreased (P<0.05) in the hippocampal CA1.4.HE Staining:Compared with the the control group, model group have no significance (P>0.05) in the hippocampal CA1、CA2、CA3、CA4after radiation.And model+DXM in treatment group compared with model group have no statistically difference (P>0.05)in the hippocampal CA1、CA2、CA3、 CA4after DXM treatment.The control group+DXM in intervention group compared with the control group have no difference(P>0.05)in the hippocampus.5.GFAP immunohistochemistry:Compared with the the control group,model group is statistically upregulated(P<0.05)in the hippocampal CA1、CA2、CA3、 CA4.model+DXM in treatment group compared with model group have a statistically downregulation(P<0.05)in the hippocampal CA1、CA2、CA3、CA4. The control group+DXM in intervention group compared with the control group have significant upregulation(P<0.05)in the hippocampal CA3.6.TNF-α immunohistochemistry:Compared with the control group, TNF-α expression in model group is upregulated significantly(P<0.05),and model+DXM in treatment group compared with model group have downregulation and have statistical significance(P<0.05)in the hippocampal CA2、CA3、CA4. The control group+DXM in intervention group compared with the control group have statistical upregulation(P<0.05)in the hippocampualCA4.7.The change of BBB after radiation:Compared with the control group, Water content、EB content in brain was increased significantly in model group (P<0.01), Compared with model group, Water content、EB content in brain have statistical decrease (P<0.05) in Model+DXM in treatment group. The control group+DXM in intervention group compared with the control group have no statistical significance (P>0.05). Conclusion1. low-dose fractioned brain irradiation can bring hippocampus injury related to the change of behavior.2. DXM in treatment can be seen downregulated obviously in GFAP and TNF-a expression in the hippocampus of brain tissue. Water content and EB content in the brain have significant decrease.