| Objectives: Vascular dementia (VD) is a kind of cerebral dysfunction caused by various cerebral vascular disease, which is called the acquired intelligence impairment syndrome. The incidence of cerebral vascular disease rises year by year rapidly and heaviens the load of the society and family. At present, the pathogenesis of VD hasn't been distinct. Therefore, it is significant to study the pathogenesis of VD.It is necessary to establish a successful VD animal model for further to research the pathogenesis. In the study, we choosed mice as the experimental animal and ligated the bilateral common carotid arteries for ischemia- reperfusion three times to establish the VD model. And the learning and memory function were evaluated through step-down test and water maze test.The hippocampus is considered to be closely correlated with learning and memory. It is reported that synaptic plasticity plays an important role in learning and memory, and decreaseing the number of synapse and changing the construction of synapse have closely related to learning and memory. It is reported that there are ultrastructural changes in the area of hippocampal CA1 in VD. There are condensed nucleus, reduced cytoplasmic organelles, edematus neuron and reduced synapse. On these bases, the study made further to observe the synapse of CA1 by transmission electron microscopy (TEM), to offer more morphological evidences for VD.The lateral recess of fourth ventricle is one of the specific areas in the circulation of cerebrospinal fluid and the important site in the chemical signal transduction in brain. It has the superintend function to the immunity information molecule, and participate in regulating of neuronal secretion and neuronal immunity to mantaining the balance of the internal environment. It is reported that there are neurofibril tangling(NFT) and amyloidosis in the ependyma of the ventricles in Alzheimer's disease(AD). The quantity of cilia and microvilli is decreased apparently in the lateral recess of fourth ventricle in VD. A number of secretory vesicles with different size and shape could be observed over the ependyma. The decreased neuron-like cells become shrinked with fewer dendrite. On these bases, the study made further to observe the ependyma of the lateral recess of fourth ventricle through scanning electron microscopy (SEM), to investigate the pathogenesis of VD.Methods: The study inculds three parts1 The mice of the VD model were subjected for ischemia-reperfusion by ligating the bilateral common carotid arteries three times to establish the VD model. In 29th/30th day after operation, the learning and memory function of every group were tested through step-down test and water maze test.2 The mice's brains were fixed up by 3% paraformaldehyde and 1% glutaraldehyde solution. The ultrastructural changes in the hippocampal CA1 were observed through TEM.3 The mice's brains were fixed up by 3% paraformaldehyde and 1% glutaraldehyde solution. The ultrastructural changes in the lateral recess of fourth ventricle were observed through SEM.Result:1 The evaluation of behavior of the two groups mice1.1 In 29th day after operation, the learning function of every group was tested by step-down test and water maze test.(1) The results of step-down test revealed that:â‘ The response time of the VD model group prolonged distinctly (P<0.01), compared with the sham- operated group.â‘¡The error times of the VD model group increased notably (P<0.05), compared with the sham-operated group.(2) The results of water maze test revealed that:â‘ The swimming time of the VD model group prolonged distinctly (P<0.01), compared with the sham- operated group.â‘¡The error times of the VD model group increased notably (P<0.01), compared with the sham-operated group. 1.2 In 30th day after operation, the memory function of every group was tested by step-down test and water maze test.(1) The results of step-down test revealed that:â‘ The latency time of the VD model group shortened distinctly (P<0.01), compared with the sham-operated group.â‘¡The error times of the VD model group increased notably (P<0.01), compared with the sham-operated group.(2) The results of water maze test revealed that:â‘ The swimming time of the VD model group prolonged distinctly (P<0.01), compared with the sham- operated group.â‘¡The error times of the VD model group increased notably (P<0.01), compared with the sham-operated group.2 The ultrastructural changes of the neuronal synapse in the hippocampal CA1 by TEM.(1) In the sham-operated group, there were many synapses in the area of hippocampal CA1. The mitochondria and synaptic vesicles were assemblaged in the presynaptic membrane, the synaptic cleft was clear and the postsynaptic dense material(PSD) was thick.(2) In the VD model group, the mitochondria were swollen and reduced, and the mitochondrial crista were lost or coalesce. The number of synaptic vesicle was reduced apparently, the synaptic cleft was cloudiness and the PSD was thinner.3 Features of ependyma in the lateral recess of fourth ventricle by SEM(1) In the sham-operated group, the arrangement of ependyma of the fourth ventricle was in order, and there were abandant cilia and microvilli on its surface and rare secretory vesicles.(2) In the VD model group, the quantity of cilia and microvilli on the surface of ependyma was reduced obviously. Both of them became disorder. The surface of ependyma cell became rugosity, even a lot of coloboma in it. The silt-like secretion covered the ependyma cell, and many cilia impressions in it. And meanwhile, a number of secretory vesicles of different size and shape could be observed over the ependyma. Conclusion:1 The study successfully established the VD mice model which could imitate the cognitive impairment of VD in clinic. The VD model is a perfect animal model and feasible to study the VD.2 The number of synapse was reduced and the constitution had the pathological changes in the hippcampal CA1 area of VD mice. These changes impaired the nerve impulse transmission, and might be one part of the pathogenesis of VD.3 The quantity of cilia and microvilli reduced, the silt-like secretion and lots of coloboma on the surface of ependyma cell in the lateral recess of fourth ventricle in VD mice. The ultrastructural changes impaired the ependyma cell metabolism and function, these might participate in the pathogenesis of VD. |
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