Pharmacological studies to evaluate a model for vascular dementia

各种动物模型已被用于研究在人类痴呆中观察到的行为和病理生理学变化，并进一步阐明推定的抗健忘药的活性。尽管人们普遍认为人类痴呆症中存在进行性认知功能障碍，但在这些动物模型中观察到的认知缺陷通常是短暂的，并以时间依赖性方式恢复到正常水平。本研究通过观察双侧颈总动脉（2 VO）永久性阻断对大鼠学习记忆能力、脑组织病理学改变和基因表达的影响，探讨2 VO大鼠作为血管性痴呆模型的可行性。2）2 VO后早期大鼠大脑皮质和海马白色物质稀疏，神经元皱缩，MAP-2免疫反应性降低，GFAP免疫反应性增强。3）分离出2 VO诱导的表达变化相关基因。vof-16（Accession No.AB006881）的表达增强与八臂径向迷宫任务检测到的记忆缺陷相关，总之，2 VO大鼠似乎是研究人类痴呆的病理生理学和阐明这种疾病的药物治疗潜力的有用模型。

A variety of animal models have been used to investigate the behavioral and pathophysiological changes observed in human dementia, and to pharmacologically elucidate activities of putative anti-amnesiac drugs. Although it is generally accepted that progressive cognitive dySfunction occurs in human dementia, cognitive deficits observed in these animal models are usually transient and recover to a normal level in a time-dependent manner. In this study, we investigated the influences of permanent occlusion of bilateral common carotid arteries (2VO) in rat on learning and memory performance, histological changes in brain and gene expression changes to evaluate the 2VO rats as a model for vascular dementia.1) The results from the 8-arm radial maze task show that 2VO disrupted both working and reference memory. Tacrine, a cholinesterace inhibitor, improved the working memory deficit.2) 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in cerebral cortex and hippocampus at early stage after 2VO.These histological changes were accompanied by a decrease in immunoreactivity for MAP-2 and increase in GFAP immunoreactivity. Shimotsu-to, a Kanpo medicine, and GST-21, a nicotinic acetylcholine receptor agonist1 had protective effects on these histological damage induced by 2VO.3) Some kind of genes which changed the expression by 2VO were isolated. The expression enhancement of a novel factor named vof-16 (Accession No. AB006881) had a correlation with memory deficit detected by 8-arm radial maze task.Taken together, the 2VO rat appears to be a useful model for investigating the pathophysiology of human dementia and to elucidate the therapeutic potential of drugs for this disease.