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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

由于我们对岛根县老人之家的囚犯进行的流行病学调查表明，超过一半的老年痴呆症尸检病例是脑血管痴呆症，本研究以100%自发性卒中的易卒中SHR（stroke-prone SHR，SHRSP）和OM/DM杂交，建立脑血管性痴呆动物模型。在从美国NIH引进的24株正常血压菌株中，以ADP聚集法测定血小板功能的N株最快。从具有中等血压和血小板功能的Fl杂种，我们获得了F2代，其显示出血压和血小板聚集的广泛变化。F3进一步从具有中度高血压和加速血小板功能的F2中获得，通过将具有接近SHRSP的高血压和具有接近OM/N的血小板功能的F3进行杂交，我们获得了F4代，其中我们观察到由于多发性脑梗死导致的腔隙性卒中。 ...更多信息 n尸检病理检查。这些F4后代的病理学接近于人类脑血管痴呆，这些大鼠暂命名为SPOM大鼠。详细的电子显微镜检查显示，这些大鼠的穿通动脉最初表现为外中膜病变，被认为是局灶性变性和坏死，后来扩展到整个中膜。巨噬细胞粘附在内皮细胞上，破坏紧密连接，破坏血脑屏障，侵入内膜下，引起大量纤维蛋白浸润和沉积，导致管腔狭窄和血栓形成。被动回避实验表明，这些SPOM表现出明显的行为障碍。因此，SHRSP与OM/N杂交选育出的SPOM新品系可作为人类脑血管性痴呆的病理和行为学模型，并可在该模型上进一步研究脑血管性痴呆的防治。少