| Cerebral vascular disease is one of the most important diseases which are harm to our health. Ischemic cerebrov- ascular disease accounts for 70% cerebral vascular disease and possesses the specialty of high incidence of a disease, the disabled and recrudescence. Chronic cerebral ischemia is a common pathological status in nervous system, it accompanied with many cerebrovascular diseases, such as cerebral arteriosclerosis, Vascular dementia (VD), Alzheimer's disease (AD), Arteriovenous malformation. Cognitive impairment is the main clinical situation in earlier period of chronic cerebral ischemia, and then the permanent neural impairment. Its pathogenesis is different from acute cerebral ischemia.β-Amyloid peptide(Aβ) is a key factor in the pathogenesis of AD. Through the loss of Ca2+ homeostasis, the generation of oxidative stress and the enlargement of excitatory toxicity, Aβcan induce neuronal degeneration and the generation of dementia. Recently, many trials have indicated Aβdeposits in hippocampus and cortex after cerebral ischemia. But most of them are the results in the different period of acute ischemia. Recently, it is reconstred that the free radicle which is induced by Aβmediates neuronal oxidative damage hypothesis. So it is very important to manufacture the durg which can reduce generation of Aβand anti-oxidative damage for preventing AD and cerebral ischemia.Grape polyphenols (GP) is also called grape procyanidin (GPC), is a natural plant which contains active polyphenol materiae. It is extracted from grape seed and grape peel, and considerd as a good protecting from oxidation. At present, some studies have confirmed that GPC can applicate to treatment and precention of myocardial ischemia-reperfusion injury through clearing oxygen free radical in vascular endothelial cell of ischemia. From the pharmacomechanism and pathogenesy of cerebrovascular disease, GPC could have good effect on ischemia cerebrovascular disease. But there are not researches about this yet, especially the studies of the effect on brain protection during chronic cerebral ischemia.So in this study we observe the expression of Aβ1-42 and explore the protective effect of natural antioxidant-GPC following chronic cerebral ischemia which provides the evidence for illuminating the effect of therapy and brain protective mechanisms of GPC.We adopted the permanent bilateral carotid arteries occlusion (2VO) in male Wistar rats to produce the chronic cerebral hypoperfusion. 72 rats were random divided into 4 groups after initial screening:blank control group, sham operation group, operation group and GPC treatment group. According to the changes of weight, GPC treatment group were fed by 250 mg/kg/d GPC and the weight were test every week. Morris water maze experiment tests the rats'memory change of each group of different time after 2VO (2,4,6 month). Brain samples with HE staining to observe the changes of nerve cell in each group rats'hippocampus CA1 region with light microscopic methods; the changes of Aβ1-42 by the immunohistochemical methods were observed. Explore brain damage of chronic cerebral hypoperfusion and protection of GP through evaluating Behavioral changes and Pathological changes of therapy group and operation group at 2 months, 4months and 6onths after 2VO.The results are as follows:①Behavioral changes. The rats with CCA occlusion performance showed their memory ability decreased from 2 month after operation, and with the time going, this situation become more seriously. But the intelligence of every treatment group has obviously improved. ②Pathological changes. With the time of the chronic cerebral ischemia going, the degenerating, necrosis and detachment of neuron could be seen in hippocampus CA1 region, even the pyramidal layer disappeared. GPC can significant lessen this damage.③The immunohistochemical changes. From the immunohistochemical slices, we saw there was a gradual increase in number of Aβ1-42 in hippocampus CA1 region after the occlusion of bilateral carotid arteries with the prolongation of ischemic time. Compare with the operate group, number of Aβ1-42 decreased obviously in the treatment group.From the whole experiment we can conclude: Natural antioxidant-Grape Procyanidin can significant improve progressive cognition impairment of the rats, lessen neuron damage, reduce the expression of Aβ1-42 in hippocampus CA1 region following chronic cerebral ischemia by permanent occlusion of bilateral common carotid arteries. GPC may be through clearing oxygen free radical to protect neuron to avoid the neurotoxicity of Aβ.
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