Danshensu Alleviates Neuron Damage In Vascular Dementia Mice Via Improving Cerebral Microcirculation

Objective:Vascular dementia refers to cerebral dysfunction induced by various cerebrovascular diseases.Moreover,the pathogenesis of vascular dementia is not clear.Clinical studies show that the regions of frontal cortex and hippocampus with declining blood flow in patients with vascular dementia.Therefore,chronic cerebral hypoperfusion causes of declining blood flow,which is one of the major mechanism of vascular dementia.Danshensu,one of the major components of salvia miltiorrhiza,that contribute to dilate coronary artery,reduce platelet accumulation,protect endothelial cells,improve microcirculation disturbance,to name a few.TCM,particularly salvia miltiorrhiza,are used to therapy the dementia in ancient times.To study the possible pathogenesis of DSS on cognitive function impairment and dyskinesia in mice after chronic cerebral hypoperfusion by observing its effects on improving and discussion its mechanism.Methods:By using C57BL/6J mice subjected to left common carotid artery permanent ligation causes of cerebral chronic hypoperfusion.Mice are divided into the control group,model group(CCH group),DSS group and Ozagrel group.Morris water maze is used to examine the learning and memory function.Beam balance test is used for estimating motor function.Nissl staining is used to observe typical neuropathological changes in hippocampus,frontal cortex and parietal cortex.Immunohistochemistry is used to evaluate to microvascular density and the level of VEGF expression in hippocampus,frontal cortex and parietal cortex.Results:The ability of learning and memory are estimated by Morris water maze in each of group:navigation test shows that the Model mice have significantly difference in escape latency as compared with Sham.Spatial probe experiment shows that in model group,the time spending in the quadrant where the hidden platform was previously placed was significantly shorter than that in the sham group.However,the decreased time in Model group was significantly increased by DSS administration.The diagrams of search trajectories in Morris water maze on day 4 of acquisition,which the Model mice have longer trajectories in the quadrant where the hidden platform was removed than the DSS mice.Beam Balance Test shows that the Model mice have significantly increase of footfaults as compared with Sham mice.On the other hand,in the model group,the time spending in the beam is significantly longer than that in the DSS group.Nissl staining revealed that after unilateral carotid artery ligation,the number of normal neurons,including in CA1,frontal cortex,parietal cortex,of Model group sharply decreased,while the while the relict neurons showed karyopyknosis,anachromasis,nucleoli disappeared and vacuolization.In contrast,in the DSS group,significantly increased the number of pyramidal cell that include CA1,frontal cortex and parietal cortex.The immunohistochemical results show that DSS can significantly increase the microvascular density,which is in CA1,frontal cortex,parietal cortex,after chronic cerebral hypoperfusion.In addition,treatment with DSS significantly improved the expression of VEGF in CA1,frontal cortex,parietal cortex of mice.Conclusion:DSS significantly alleviates the dyskinesia and impairment of cognitive in chronic hypoperfusion mice.DSS able to lighten the degree of damaging neurons after chronic hypoperfusion.DSS is capable of increasing expression of VEGF and MVD after chronic hypoperfusion.DSS helps to reduce the microcirculation disturbance in chronic hypoperfusion mice.