Microvascular changes in aged rat forebrain. Effects of chronic nimodipine treatment.

In the present study the effects of long-term treatment with the 1,4-dihydropyridine calcium antagonist nimodipine on ultrastructural alterations of the microvascular morphology were examined in the frontoparietal cortex, entorhinal cortex and CA1 of the hippocampus in the aged rat. Qualitative observations of cerebral microvasculature of aged (30 months) Wistar rats revealed the presence of microvascular fibrosis, membranous inclusions within the basement membrane and basement membrane thickenings. In several cortical regions the percentage of aberrant microvessels was significantly reduced in the nimodipine-treated rats. The observed microvascular anomalies were classified into five distinct categories of which microvascular fibrosis type II, defined as collagen deposits up to 1 micron within the microvascular basement membrane, showed the strongest reduction in the nimodipine-treated cases. The decrement of the percentage of aberrant microvessels and the relative occurrence of several classes of microvascular deviations showed some variation in the various brain regions examined and was most pronounced in frontoparietal cortex layer III. These results may provide a morphological basis for the improved motor and cognitive performance in aged rats after long-term oral nimodipine administration.