Study Of Cerebral Blood Flow, Pathology And Cytokines In Vascular Dementia Rats Induced By Chronic Cerebral Ischemia

Dementia is a common disease which is severely harmful to the physical and mental health of the elderly, as well as a heavy load not only to the society but also to the family. As we can see from the survey which was made in eleven provinces of our country, prevalence rate of vascular dementia is 324/1 million persons among the elderly over sixty years old, while 238/1 million persons in Alzheimer's dementia and vascular dementia is the most common dementia of all the dementia. So it's very valuable to study the pathophysiological mechanism of VD and to look for some effective ways to prevent and cure the disease.At present, the exact reason resulting vascular dementia is not very clear and was thought mainly due to multi-infarct dementia, while the most recent research suggest that the chronic hypoperfusion of many cerebral regions probably be the main reason of vascular dementia. Recently many trials has indicated that IL-1β,IL-6 and TNF-αare three main cytokines which are involved in the ischemic injury. But most of them are about acute ischemia and there is very few trial on chronic ischemia. And there is no any report on the chronic ischemia of so many cytokines in different time. We adopted the permanent occlusion of bilateral carotid arteries in male Wistar rats to produce the chronic forebrain ischemia which was similar to the human chronic cerebral ischemia. We estimated the performance of the rats in the Morris water maze tests. The neuropathology changes were inspected by light microscopic examination. The laser Doppler was used to assess the cerebral blood flow changes of the rats. Besides, we observed the changes of IL-1,IL-6 and TNF by the immunohistochemical methods. Here are the results. 1. rCBF changes. After the operation the rCBF of the frontal lobe , parietal cortex ,hippocampus and subcortex reduced to 20.91%, 52.76%, 71.80% and 67.86% of the control group respectively, then recovered slightly at the time of the 2nd and reduced again . At the time of 4th week, the rCBF was evidently lower than the control group, too. The chronic and steady reduction of rCBF in the rats which has been dementia induced by the permanent occlusion of bilateral carotid arteries is very similar to the reduction of rCBF of the patients of VD. So we thought the model induced by the permanent occlusion of bilateral carotid arteries is a better model to research VD.2.Behavioral changes. Before the occlusion of bilateral carotid arteries the rats had been trained to find the platform under the milk water in the Morris water maze in ten minutes, but after the operation from the first month to the fourth month we found the rats became more and more foolish and some of them can not find the platform even in three minutes. So we called the rats suffered the cognitive impair. This memory dysfunction induced by the occlusion of bilateral carotid arteries is more chronic and more permanent as compared with other ischemic models and we can conclude from the results in Morris water maze tests that chronic hypoperfusion can result in chronic and permanent cognitive impair .3.Pathological changes. At the beginning, the diffused cerebral edema and exudation were apparent, then attenuated gradually. Then the degeneration and detachment of neuron could be seen, so did the necrosis of the neuron and hypertrophic neuroglial cells. We thought these pathological changes are due to chronic and steady reduction of rCBF, while not induced by acute cerebral ischemia.4. The immunohistochemical changes. From the immunohistochemical slices of IL-1β,IL-6 and TNF-α we can see there is an evident increase in number of these cytokines in frontal and temple lobe after the occlusion of bilateral carotid arteries . And this increase is the most apparent in the 24 hours or 1 weeks, then there is an gradually and slowly decrease in number of IL-1β,IL-6 and TNF-α, but it is still higher than the control rats until the 4th month. So we can conclude that chronic and steady reduction of rCBF can result in the increa...