Experiment Study On Spine Loading To Improve Learning And Memory Impairment In Vascular Dementia Rat Model

Objective Vascular Dementia(VD)is the second largest senile dementia after Alzheimer's disease,its incidence is increasing year by year.Vascular dementia is an age-related neurodegenerative disorder characterized by histopathological damage with learning and memory impairment caused by hypoxic-ischemic brain damage and has gradually become an important social issue.Chronic cerebral ischemia refers to a common pathophysiological state in which cerebral blood supply is below the physiological threshold for a long time and is the pathological basis of many ischemic cerebrovascular diseases and eventually leads to cognitive dysfunction.Vascular dementia refers to cognitive dysfunction syndrome caused by ischemic cerebrovascular disease.Cerebral insufficiency is an important cause of vascular dementia,and the degree of decrease of cerebral blood flow is related to the decrease of learning and memory ability after brain injury.Mechanical loading can simulate the active motility of human body to some extent with a mechanical stimulation to the spine in a certain loading frequency,and regulate certain metabolic pathways.The preliminary work proves that in the animal model of osteonecrosis of the femoral head,mechanical loading treatment can promote the angiogenesis of the injured site,but little research has been done on the protective effect of mechanical loading on vascular dementia.In this study,VD rat model was established to observe the effects of mechanical loading on learning and memory ability of vascular dementia rats and the recovery of neurons after ischemic injury to explore the protective effect of spine loading on vascular dementia,providing a new idea for the rehabilitation treatments of vascular dementia.Methods Twenty-seven healthy male Sprague-Dawley rats were randomly divided into Sham group,vascular dementia model group(VD group)and spine loading treatment group(VD + L group),with 9 in each group.Sham group was isolated only from the common carotid artery but not ligated.The VD model was established by permanent ligation of the common carotid artery in the VD group and spine loading was conducted in the VD + L group for 5 weeks.After treatment,Morris water maze test was used to test the learning and memory abilities of rats in each group.After the behavioral test was finished,samples were prepared for subsequent experiments and the pathological changes of brain tissue were observed by HE staining and Nissl staining.The expression of glial fibrillary acidic protein(GFAP)was assessed by immunohistochemistry and western blot.Results 1.Effects of spine loading on learning and memory in rats In the Morris water maze positioning navigation experiment,the escape latency of rats in each group decreased significantly with the increase of training time.The escape latency of rats in VD group was significantly longer than that in Sham group from 2d,while the escape latency of VD + L group was significantly shorter than that of VD group,but still longer than Sham group(P <0.05).In the Morris water maze space exploration experiments,the number of crossing platform and staying time in VD group were significantly lower than that in Sham group in 120 s while that in VD + L group were significantly longer than that in VD group,but still lower than Sham group(P <0.05).2.Effects of spine loading on pathological changes in rat brain.The results of HE staining showed that hippocampal neurons in Sham group had a complete structure with clear nucleolus and large nucleus.The hippocampal neurons in VD group had a loss of structure,poor resolution,scattered arrangement and poor survival status.Compared with VD group,VD + L group neurons morphological structure integrity,survival improved significantly,arranged neatly.The Nissl staining of hippocampal CA1 region and cerebral cortex showed that the number of pyramidal cells in Sham group was full,distributed evenly,arranged neatly,and the structure was complete.The number of pyramidal cells in VD group was significantly decreased compared with Sham group,Irregular shape.Compared with VD group,the pathological damage of neurons in VD + L group was significantly reduced,the cell survival state was significantly recovered,the number of pyramidal cells was significantly increased(P <0.05).3.Effects of spine loading on astrocytes activation in rat brain The results of immunohistochemistry: Compared with Sham group,the number of GFAP positive cells in hippocampus and cortex of VD group was significantly increased,and the cell body was larger.Compared with VD group,the number of GFAP positive cells in hippocampus and cortex of VD + L group was significantly decreased(P <0.05).The results of western bolt: Compared with Sham group,the expression of GFAP in hippocampus and cortex of VD group was significantly increased.Compared with VD group,the expression of GFAP in hippocampus and cortex of VD+L group was significantly lower(P<0.05).Conclusion 1.The results of this study show that mechanical loading can significantly improve the learning and memory impairment of VD rats and protect the neurons after ischemia.The therapeutic effect may be related to mechanical loading to reduce the pathological damage of hippocampus and cortical neurons and inhibit the activation of glial cells.2.This study provides a new idea for the rehabilitation of vascular dementia and provides a theoretical basis for the clinical application of mechanical loading therapy in the future.