FORMATION OF CEREBROVASCULAR ANOMALIES IN THE AGING RAT IS DELAYED BY CHRONIC NIMODIPINE APPLICATION

At the ultrastructural level two main categories of microvascular anomalies can be distinguished in the aged rat brain. These categories comprise [1] membranous inclusions within the basement membrane and [2] microvascular deposits, which include microvascular fibrosis and thickening of the basement membrane (BMT). In this study we examined the percentage of microvessels displaying ageing-related malformations in the frontoparietal motor cortex of rats aged 16, 24, 30 and 32 months. The percentage microvessels with membranous inclusions and microvascular deposits both gradually increased until the age of 30 months, after which no further increase was observed. The percentage fibrotic microvessels, however, increased until the age of 30 months, but was decreased at 32 months. This decrease of fibrotic microvessels at 32 months coincided with a proportional increase of cerebral microvessels provided with a thickened basement membrane. Combined with qualitative observations these data suggest that in a very late stage of the ageing process collagen fibrils in microvascular fibrotic plaques are depolymerized and degradated. By this mechanism it appears that microvascular fibrosis is transformed into basement membrane thickening. Long-term application of the calcium entry blocker nimodipine did not influence the amount of microvessels with membranous inclusions within the basement membrane, but in contrast resulted in a prominent reduction of ageing-related microvascular deposits when administered from 24 to 30 months. The effect of a prolonged nimodipine treatment from 24 to 32 months on the amount of microvascular deposits was still significant, however, much less conspicuous. We now conclude that chronic administration of nimodipine delays the formation of microvascular deposits up to the age of 30 months. Furthermore, the beneficial effect of nimodipine treatment from 24 to 30 months on microvascular integrity is not accompanied by a reduced systolic blood pressure.