| Background and Objectas the standpoint that long-term chronic cerebral hypo perfusion can lead to kinds of neurodegenerative diseases be confirmed by a great quantity of experimental data, people begin to focus on the chronic cerebral hypo perfusion more and more frequently. chronic cerebral hypo perfusion keep close contact with cognitive deficiencies of aging people and AD patients. AD is an insidious progressive and complex neurodegenerative diseases which can affect multi-regions of central nervous system. AD accounts for the vast majority of dementia, and one of its most striking features is the global cognitive disability. Indeed, vascular factors play a critical role in the pathogenesis of AD. Perfusion deficiencies are present from the very early pre-clinical phases of AD (mild cognitive impairment (MCI)) and persist well into the latest stages of the disease, demonstrating a pattern of increased hypoperfusion with disease development. This phenomenon, over time, yields catastrophic consequences on brain structure, function, and cognition, leaving the patient irreversibly impaired, especially in their memory faculties. Perfusion disorders are considered to be the incentive reason of most mental diseases and neurodegenerative diseases. A sudden decrease of cerebral blood of the special part of brain may lead to infarction occurred, but the long-term hypo perfusion is the vital component of memory loss and the dementia progress. The extract correlation between AD and the cerebral hypo perfusion have already been clarified. AS there is no effective and straightforward treatments especially target to AD have been found so far, ameliorate the cerebral hypo perfusion state may be the new treatment target spot of AD. The Number and morphology of dendritic spine and synaptic plasticity is very important to the the formation and maintain of normal cognitive which including studying and memory. Vast compelling evidence suggest that Rho-family GTPases play essential roles in orchestrating the development and remodeling of spines and synapses plasticity. and the protein Cdc42 is one of the most important member of the Rho family. Cdc42,a key regulators of the actin cytoskeleton, can play a significant part in regulating physiology activities including cell differentiation migration spine branching and morphology structure. the mutation or low expression of Cdc42 will have negative effects on the outgrowth of dendritic spines and synaptic and then lead to cognitive deficiencies. Also the abnormal of any protein of the Cdc42 pathway will have the same effect as above.Bilateral permanent carotid artery ligation (2VO) is the most popular method to simulate the state of the chronic cerebral hypo perfusion to study various kinds of central nervous system diseases like Vascular dementia and Alzheimer’s disease, masses of studies have already revealed the conclusion that compared to the normal control group animals,the 2VO model group animals have a obvious decrease in the ability of studying and memory.So, in this experiment, we prepare to handle the rats with the 2VO surgery to imitate the chronic cerebral ischemia state in adult human, and investigate the possible relationship between the expression of cell division cycle 42 GTP-binding protein(Cdc42) and the cognitive deficiencies in the cerebral blood flow deduction state of the rat hippocampus.Method1. Forty SD rats were equally divided into 4 groups:Sham operation control group and 2-VO model groups(permanent ligation of bilateral common carotid arteries for 8,10 and 12 weeks, respectively).2. handle the 2VO model rats with permanent ligation of bilateral common carotid arteries, and handle the sham-operated group as same as the 2VO model groups rats except occlude the bilateral common carotid arteries. 3. use Morris water maze to detect the cognitive function of the rats including learning and memory.4. The brains were taken at week 8,10 and 12 after the establishment of models for measuring the expression of Cdc42 protein using immunohistochemistry.5. The brains were taken at week 8,10 and 12 after the establishment of models for measuring the expression of Cdc42 protein using western blotting.6. The statistical package for the social sciences(SPSS) were used to analyze the data obtaining.Results1. In the Morris water maze, the model group rats needed more escape time than the control group, and they did not swim longer in platform quadrant crossing than in the others in the Morris water tests (P<0.05).2. the Cdc42 positive cells on hippocampal areas in the model rats was significantly deducted than in the control rats(P<0.05).3. the expression of Cdc42 on hippocampal areas in the model rats was significantly decreased than in the control rats(P<0.05).Conclusionsas the ischemia state prolong, the cognitive deficiencies of the rats become more and more serious, and at the same time the expression of Cdc42 decrease dramatically this phenomenon may suggest that there are some correlations between Cdc42 and the cognitive deficiencies. |
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