| Chronic cerebral ischemia have already been considered as a common pathological mechanism of various diseases such as vascular dementia , Alzheimer's disease and Binswanger's disease. There are a lot of reasons lead to cerebral circulation insufficiency , such as cerebral atherosclerosis caused by hyperlipidemia , cerebral arteriolosclerosis caused by hypertension, disturbance of cerebral microcirculation caused by hyperglycaemia. All of them could make for the birth and development of chronic cerebral ischemia, different pathological damage of brain. In the past, people adopted the permanent occlusion of bilateral common carotid arteries (2VO) to produce the chronic cerebral ischemia models , which could reduce Wistar rat's cerebral blood flow obviously after model seted up several month. Cerebral blood flow in different region of rat brain descended differently. After this a series of research have been reported that chronic cerebral hypoperfusion result from 2VO could lead to brain damage. Such as the degeneration and loss of neuron in cortex and hippocampi, the damage of rats'spatial learning and memory ability. However, several diseases lead to chronic cerebral ischemia in human body, such as hyperlipidemia, hypertension, diabetes mellitus. Model of 2VO could decreased cerebral blood flow significantly in hemodynamics, but whether pathological changes caused by hyperlipidemia, hypertension and other diseases will affect chronic cerebral ischemia? What caused this change? It would be difficult to carry out if used only this model. Thus, if we could improved the model of 2VO, added hyperlipidemia on the basis of it, and research on , we will reveal the pathological changes of chronic cerebral ischemia in truly human body more closer.In this experiment, the hyperlipidemia with chronic cerebral ischemia animal model was established to study the link and the interaction between hyperlipidemia and chronic cerebral ischemia. Males Wistar rats weighing 250～300g were randomly divided into normal group, operation group, high-fat group and high-fat with operated group. Rats of latter two groups fed with high-fat food seven weeks, then test blood lipid , which is higher than normal one is the successful establishment of model. After that, permanent ligation of bilateral common carotid arteries(2VO) was used to produce the chronic cerebral ischemia model. Morris water maze was used to measure at different time points (after one month, two months, four months) rats in each group (normal group, operation group, high-fat group and high-fat with operation group) learning and memory function. through stained of HE, observing neurons morphological changes of hippocampal CA1 region of rat. To measure expression of ICAM-1 in hippocampal CA1 region of rats in different group, the immunohistochemical methods was used.The result showed: behavioral test results showed that: The rats with common carotid ligation performance showed their spatial learning and memory ability decreased from 1 month after operation, and with the time going, to 2 and 4 months, this situation become more seriously. The ability of spatial learning and memory decline more serious in high-fat with operation group, rather than any other group. Pathological changes: The degeneration, necrosis and detachment of neuron in hippocampus could be seen in the rats of experimental group, the gap of perivascular become larger and a amount of inflammatory cell infiltration. The longer the ischemic time goes by, the worse the neurological damages. In 4 months experimental group, we observed serious lose of neurons. In all times all groups, the pathological changes of high-fat with operation group was most serious. Immunohistochemistry: We could not find any ICAM-1 positive vascular and cell of hippocampal CA1 area in normal group, reversely, the expressional level of ICAM-1 increased gradually from 1 month to 2 months in other three groups, and mainly express on the surface of endothelial cell. With time goes by, the damage of endothelial cell aggravately and glial cell hyperplasia,until 4 months ICAM-1 express on the surface of nerve cell surface (mainly glial cells).This study indicates that nerval damage caused by chronic cerebral ischemia not only because the reduction of blood flow, but the pathological changes resulted from hyperlipidemia could also lead to it. This damage would be more serious. The mechanism of injury is mainly because the increasingly expression of ICAM-1 lead to immune inflammatory response which contributed to the nerval damage. ICAM-1 express on the surface of endothelial cell, until endothelial cell totally damaged and glial cells hyperplasia in 4 months, the latter one continue the responsibility.From the whole experiment we can conclude:1. Both hyperlipidemia and chronic cerebral ischemia can lead to cognitive dysfunction, and exacerbated with time past. When hyperlipidemia with chronic cerebral ischemia, the cognitive dysfunction would been significantly increased.2. Both hyperlipidemia and chronic cerebral ischemia can lead to the injury of capillary vessel and hippocampal neuron, and exacerbated with time past. When hyperlipidemia with chronic cerebral ischemia, the injury would been significantly increased.3. The up-expression of ICAM-1 contribute to the nerval damage, which caused by hyperlipidemia, chronic cerebral ischemia and hyperlipidemia with chronic cerebral ischemia.
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