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

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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