Research On The Mechanism Of Action Of Vascular Dementia And Analysis Of Clinical Features Of Vascular Dementia

Part I Research on The Mechanism of Vascular DementiaObjective:Vascular dementia(VaD)is the second largest type of dementia which influenced the life quality of patients seriously,and brought a heavy burden to society and family.This research examined the changes of behavior,the damage of neuronal cells in hippocampus,and the activation of glial and the change of vascular endothelial cell on rat VaD model,and studied the mechanism of VaD.Methods:40 healthy male Sprague Dawley rats weighing 250-300g were selected.The rats models of VaD were made by permanent occlusion of bilateral common carotid arteries(2VO).The sham groups separated carotid arteries without ligatured.Rats were divided into four groups randomly:hypoperfusion 3 months sham-group,hypoperfusion 3 months VaD-group(2VO 3 month),hypoperfusion 6 months sham-group,hypoperfusion 6 months VaD-group(2VO 6month).At 3 and 6 month after the operation,the behavioral experiment was examined,then the rats were sacrificed and their brains were removed for the following test.The neuron specific nuclear protein(NeuN),glial fibrillary acidic protein(GFAP),ionized calcium binding adapter 1(IBA-1),and platelet endothelial cell adhesion molecule 1(PECAM-1)were used as markers of the neurons,astrocytes,and microglial cells,endothelial cells in hippocampal CA1 region,respectively,and detected by immunohistochemistry.The expression level of Wnt3a??-catenin?p-GSK-3?,GSK-3? in hippocampus were detected by western blot analysis.Results:The locomotor activity and the ambulatory time increased in the hypoperfusion 3 months VaD-group compared with sham groups(P<0.05),and obviously decreased in the hypoperfusion 6 months VaD-group(P<0.05).The number of neurons in the VaD groups were significantly reduced,and the number of neurons decreased even more significant in the hypoperfusion 6 months VaD-group(P<0.01).In the hypoperfusion VaD-groups,GFAP+astrocytes and IBA-1+Microglial cells were markedly increased(P<0.05);And the expression of GFAP+ astrocytes in hypoperfusion 3 months VaD-group was higher than that of in the 6 months group(P<0.05).PECAM-1+ staining were markedly increased in hypoperfusion 3 months VaD-group than that of hypoperfusion 6 months VaD-group(P<0.05).Moreover,the expression level of Wnt3a??-catenin.p-GSK-3? were significantly decreased in hypoperfusion VaD-group compared with the sham group(P<0.05).Conclusion:This study found that the VaD model with permanent occlusion of bilateral common carotid arteries caused neuroethology changes,injury of the hippocampus neuron,which were closely related to the activation of glial cell,and damage of vascular endothelial cell,especially after 3 months of hypoperfusion,the glial cells and PECAM-1 immune activity significantly increased.And the expression of PECAM-1 significantly decreased after 6 months of continuous hypoperfusion.After 3 months of hypoperfusion,the protein expression of Wnt3a/?-catenin was significantly reduced.The results indicated that the activation of Wnt3a/p-catenin could be negatively correlated with the activation of glial cells and the increase of PECAM-1 immune activity after VaD.Part II The Clinical Feature Analysis on Vascular DementiaObjective:To explore the clinical features of vascular dementia and to the related risk factors leading to the high morbidity of vascular dementia.Methods:The 86 patients diagnosed as vascular dementia were collected from January,2016 to December,2018 in the department of neurology and geriatrics,Affiliated Hospital of Yangzhou University.The data of age,gender,education,lifestyle,disease history,the history of alcohol and tobacco,BMI were collected.And the relationship with vascular dementia was analyzed.Results:The vascular dementia group had 86 cases with 52 males and 34 females,and an average age of(78.56±9.94).The normal group had 50 cases with 27 males and 23 females,and an average age of(78.56±9.94).The age of the vascular dementia group was significantly higher than that of the normal group(P<0.05).The BMI index in patients with vascular dementia was significantly higher(P<0.05).The incidence of vascular dementia was significantly higher in patients with stroke history,hypertension,diabetes,hyperlipidemia,and smoking than that in the normal group(P<0.05).And gender,education,lifestyle,drinking,etc.have little significance in increasing the incidence of vascular dementia.Conclusion:Age,BMI index,diabetes,hypertension,hyperlipemia,stroke,smoking,are associated with vascular dementia,which can provide some guiding significance for clinical diagnosis and treatment.