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

由于我们对岛根县敬老院的居住者进行的流行病学调查显示，老年痴呆症的尸检病例中有一半以上是脑血管性痴呆，因此我们开始了目前的研究，通过中风易发性SHR（SHR）之间的杂交来建立脑血管性痴呆动物模型。 SHRSP）现在100％自发中风，而我们注意到通过ADP聚集测试的血小板功能的OM/N菌株在24个中加速最快从美国NIH引进的血压正常的菌株中，我们从具有中等血压和血小板功能的F1杂种中获得了血压和血小板聚集表现出广泛变化的F2代，并且从具有中度高血压和加速血小板功能的F2中进一步获得了F3。通过在具有接近 SHRSP 的高血压和接近 OM/N 的血小板功能的 F3 之间杂交，我们获得了 F4 代，其中我们观察到由于多发性脑梗塞引起的腔隙性中风……更多 n 在死后病理学上这些F4后代的病理学与人类脑血管痴呆相似，这些大鼠暂命名为SPOM大鼠，详细的电子显微镜检查显示，这些大鼠的穿支动脉最初显示出外中膜病变，随后被认为是局灶性变性和坏死。然后巨噬细胞附着在内皮细胞上，通过破坏紧密连接并破坏血脑屏障而侵入内膜，导致纤维蛋白大量浸润和沉积。另一方面，被动回避试验清楚地表明这些 SPOM 表现出明显的行为障碍，因此，通过 SHRSP 和 OM/N 杂交建立的新 SPOM 菌株可以作为模型。人类脑血管性痴呆的病理和行为两个方面以及预防都可以在这个模型中进一步研究。