Protective Effects of Breviscapine on Ischemic Vascular Dementia in Rats

Abstract

With an increase of elderly population, aging-related diseases such as hypertension, arteriosclerosis and different forms of dementia are also increased. 1) One of these diseases is vascular dementia (VD). VD is a step-wise deterioration in intellectual powers that appear as different areas of the brain are damaged by loss of blood supply.2,3) The conventional concept of VD is that of multi-infarct dementia, 3,4) arising from chronic cerebral ischemia and various vascular changes in the brain.5) It is reported that the reduction in cerebral blood flow and abnormal energy metabolism occurred in chronic cerebral ischemia can induce the accumulation of NO and ROS which lead to neurons injury in selective, vulnerable regions of the brain, especially the hippocampus and cerebral cortex, accompanied by cognitive decline and some motor disorders. [6][7][8] In oriental medicine, many traditional Chinese drugs have been used clinically for treatment of ischemic cerebrovascular disease. 9) Breviscapine is extracted from the traditional Chinese drug Erigeron Breviscapus (vant.) Hand.-Mazz and mainly composed of Scutellarein, Plantaginin and Pyromeconic acid. 10,11) The injection preparation of breviscapine has been used in clinic to treat cardiovascular diseases, cerebral infarction and stroke in China. 3,10,11) The clinical reports suggested that the injection of breviscapine (0.5 mg/kg, i.v. gtt, qd, 15 d) possess neuroprotective action and improves learning and memory in cerebrovascular diseases.12,13) Although the curative effect of breviscapine in cerebral infarction and cerebral ischemia is obvious, there is no data available for this drug in treatment of VD. In this study, the effects of chronic treatment with breviscapine on the learning deficits, neuronal injury and antioxidative properties in VD rats were investigated. MATERIALS AND METHODS Animal Models and Drug AdministrationThe vascular dementia models were made from the male Wistar rats (6 weeks, 230Ϯ10 g), which were obtained from the Experimental Animals Center of Tongji Medical College, Huazhong University of Science and Technology. Wistar rats were subjected to permanent occlusion of bilateral common carotid arteries to induce chronic cerebral ischemia and mimic the VD models.14) The experimental protocols were approved by the Committee of Animal Care of Huazhong University of Science and Technology.The injection of breviscapine (Bre, Bath No. z5302066, China) was purchased from Kunming Long-Jin Pharmaceutical Co., Ltd. Tacrine (9-amino-1,2,3,4-tetrahydroacridine HCl), a reference drug for behavioral test, was purchased from Sigma (St. Louis, MO, U.S.A.) and dissolved in physiological saline. Fifteen days after surgery, the male Wistar rats were randomly divided into three groups, e.g., sham-operated group, model group, Bre-treated group and tacrine-treated group. The Bre-treated group was administered with breviscapine (2 mg/kg, i.p., equal 0.33 mg/kg adult dose, once a day). Tacrine was administered intraperitoneally at a dosage of 3 mg/kg. The sham-ope...

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Acid-Sensing Ion Channels Contribute to the Effect of Acidosis on the Function of Dendritic Cells

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