Exploitation of rat models for cerebrovascular dementia and studies on the pathogenesis and prevention.

脑血管性痴呆大鼠模型的建立及其发病机制和预防研究。

基本信息

批准号：
62480142
负责人：
YAMORI Yukio
金额：
$ 4.35万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

Since our epidemiological survey of inmates of old people's home in Shimane Prefecture indicated that more than a half of autopsied cases of senile dementia was cerebrovascular dementia, we started our present studies to establish animal models for cerebrovascular dementia by cross breeding between stroke-prone SHR (SHRSP) developing stroke spontaneously in 100% nowadays and OM/N strain in which we noted platelet function tested by ADP aggregation was most accelerated among 24 normotensive strains introduced from NIH of USA. From Fl hybrids with intermediate blood pressure and platelet function, we obtained F2 generation which showed a wide variation in blood pressure and platelet aggregation. F3 was further obtained from F2 with moderate hypertension and accelerated platelet function, and by cross breeding between F3 with hypertension close to SHRSP and with platelet function close to OM/N we obtained F4 generation in which we observed lacunar stroke due to multiple cerebral infarctio … More n at post mortem pathological examination. The pathology of these F4 offspring was close to cerebrovascular dementia in man and these were tentatively named SPOM rats. Detailed electron microscopic examination revealed that perforating arteries in these rats showed initially lesions in the outer media considered as focal degeneration and necrosis which were later extended to the whole media. Then macrophages attached on the endothelial cells and invaded into subintima by disrupting tight junction and damaging blood brain barrier to induce massive infiltration and deposition of fibrin which resulted in narrowing of lumen and occlusion with thrombosis. On the other hand, passive avoidance test clearly demonstrated these SPOM showed obvious behavioral disturbance. Therefore, a new SPOM strain established by selective breeding from the crosses between SHRSP and OM/N can be a model for cerebrovascular dementia in man both from pathological and behavioral aspects, and prevention can be further studies in this model. Less

Since our epidemiological survey of inmates of old people's home in Shimane Prefecture indicated that more than a half of autopsied cases of senile dementia, we started our present studies to establish animal models for cerebrovascular dementia by cross breeding between stroke-prone SHR (SHRSP) developing stroke sponsored in 100% nowadays and OM/N strain in which we noted platelet function tested by ADP aggregation was most Accelerated among 24来自美国NIH引入的正常菌株。从具有中间血压和血小板功能的FL杂种中，我们获得了F2的产生，该杂种显示出血压和血小板聚集的差异。从F2中进一步获得了F3，具有中度高血压和加速血小板功能，并通过在接近SHRSP的高血压和血小板功能接近OM/N的F3之间进行交叉繁殖，我们获得了F4的生成，我们在验尸检查后观察到了由于多个脑梗塞而引起的lacunar streos。这些F4后代的病理与人的脑血管痴呆接近，这些脑血管痴呆被租用命名为SPOM大鼠。详细的电子显微镜检查表明，这些大鼠的穿孔动脉最初在外部培养基中显示为局灶性变性和坏死，后来将其扩展到整个培养基。然后，巨噬细胞附着在内皮细胞上，并通过破坏紧密连接并破坏血脑屏障来诱导纤维蛋白的大规模浸润和沉积，从而导致管腔狭窄并与血栓形成闭塞，从而入侵了sibintima。另一方面，被动回避测试清楚地证明了这些SPOM表现出明显的行为灾难。因此，从SHRSP和OM/N之间的杂交中选择性繁殖建立的新SPOM菌株可以成为病理和行为方面人类脑血管性痴呆的模型，并且在该模型中可以进一步研究。较少的