小剂量海人酸导致C57BL/6小鼠产生慢性神经退行性病变  

Chronic excitotoxic neurodegeneration induced by low dose of kainic acid administration intranasally in C57BL/6 mice

作　　者：张兴梅[1] 祝捷[1] 

机构地区：[1]吉林大学第一医院神经内科,吉林长春130021

出　　处：《中风与神经疾病杂志》2006年第1期38-40,I0001,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的探索应用海人酸在C57BL/6小鼠建立慢性进行性神经退行性病变的新的动物模型。方法小剂量(3mg/kg体重)海人酸经鼻滴入C57BL/6小鼠,每3d给药1次,连续20次。观察临床表现,并应用旷场行为实验检测小鼠的行为学变化;通过Nissl染色方法评估鼠脑病理变化以及免疫组织化学方法分析小胶质细胞活化和星形胶质细胞增生情况。结果应用小剂量海人酸反复多次经鼻给药,小鼠虽无明显临床症状,但引起其皮质和海马发生兴奋性毒性所致的神经细胞退行性病变,小胶质细胞活化和星形胶质细胞增生以及行为学变化。结论此慢性动物模型的神经病理改变与人类神经退行性疾病的变化相似,因此,本文为研究人类神经系统慢性退行性疾病的发病机制及治疗提供了一个有用的动物模型。Objective To explore and establish a new animal model of chronic excitotoxic neurodegeneration induced by low dose of kainic acid （KA） administration intranasally in C57BL/6 mice. Methods All the mice were administrated with low-dose KA （3mg/kg body weight） or water as control every 2 days up to 2 months intranasally. The clinical symptoms were observed and behavioral test （open field test） was applied. Pathological changes in hippocampus and cortex were evaluated by Nissl staining and microglial activation as well as astrogliosis were detected by immunohistochemistry. Results l.ow dose of KA administration intranasally in C57BL/6 mice induced a chronic excitotoxic neurodegeneration of hippocampus and cortex in mice, without clinical signs. Microglial activation and astrogliosis also played an important role in this pathological process. Conclusion The neuropathological changes of the animal model are similar to that of neurodegenerative disorders in human,which provided a useful model to study the pathogenesis and therapy of chronic neurodegenerative diseases.

关 键 词：海人酸 兴奋性毒性作用 慢性神经退行性改变 动物模型 

分 类 号：R742.1[医药卫生—神经病学与精神病学]