The Etiological Meaning Of The Neurotoxic Lesions Of Free-radical And Glutamic Acid Induced By Chronic Cerebral Ischemic In AD

Background: It was well known that chronic cerebral ischemic was the etiology of vascular dementia (VaD). Epidemiological and clinical researches have shown a new hypothesis that cerebral hypoperfusion may be the cause of Altheimer's disease (AD).Objective: To provide experimental evidence for the new hypothesis that chronic cerebral ischemic maybe induce AD by reproducing the animal model of ligating of the bilateral common carotid arteries and showing the increasing of the expression of amyloid beta protein (Aβ) and hyperphosphorylated tau protein; showing the prolonging of the time escape latency and distance escape latency; showing the increasing concentration of serum iron, MDA, glutamic acid and Aβ.Method: 36 male Wistar rats were divided into experimental group and control group at random. According to the time of cerebral ischemic, each group was divided into 3 groups with cerebral ischemic for 12 weeks, 16 weeks and 20 weeks. According to Ohta, the bilateral common carotid arteries were ligated. The bilateral common carotid arteries of control group were only splitted but not ligated.The behavior was tested with Morris water maze at 12 weeks, 16weeks and 20 weeks respectively. The expression of Aβin serum was tested by radio-immunity and in tissue was shown by immunohistochemistry; Hyperphosphorylated tau protein was shown by immunohistochemistry; Serum iron, MDA and glutamic acid were tested by colorimetry.Results: The time escape latency and distance escape latency prolonged in the experimental group as comparing with same-age control. The longer the bilateral common carotid arteries were ligated, the more serious the symptom was. However, the results of the experiment displayed that the time escape latency and distance escape latency of the experimental group in the 16 weeks was longer than that of 20 weeks. Similarly, Serum iron, MDA, glutamic acid and Aβconcentration increased in the experimental group as comparing with same-age control. And, an inverse of serum iron, MDA, glutamic acid and Aβconcentration was also seen between 16 weeks and 20 weeks. The positive unit of Aβand hyperphosphorylated tau protein immunohistochemistical staining was higher than that of the control group. The initial Aβimmuno plaques was shown in the rats with cerebral ischemic for 12 weeks and the maturation Aβimmuno plaques was shown in the rats with cerebral ischemic for 16 weeks under higher magnification.