Abstract
Introduction: Stroke and brain ischemia are associated with macrovascular calcification. Microvascular calcification may also contribute to cerebrovascular disease, yet its prevalence and pathophysiological significance remain unclear. Hypothesis: Calcification associated with intracranial microvasculature is prevalent in elderly populations and correlates with calcification of proximal macrovascular supply. Methods: Tissues were dissected from 20 cadavers (16 female, 4 male; median age = 81 y; range = 56-94 y) unilaterally on the left side. Three vascular territories were examined representing anterior, middle, and posterior brain regions supplied by distal M4 branches of the middle cerebral artery (MCA). Proximally, two putaminal regions supplied by lenticulostriate arteries (from M1 of the MCA) were examined. Extra- and intracranial internal carotid arteries (ICA) and M1 segments of the MCA from the same subjects were previously scored for calcium; those data were used for correlation analysis. A sensitive and specific calcium detection protocol (alizarin red) was used in all studies alongside H&E. Light microscopy was performed to grade small- (< 20 micron) and large-caliber (20-200 micron) vessels for calcification. Results: Calcification was detected in all subjects, with 95% in small-caliber and 50% in large-caliber microvessels. Non-parametric Spearman correlation analysis revealed significant correlation between calcification of large-caliber microvessels in M4 (but not M1 putaminal vessels) and medial calcification of the MCA (M1 segment; r = 0.6533, p < 0.05). Contrary to our hypothesis, no correlations were found between microvascular calcification and calcification of the ICA. Additionally, no correlations were found between microvascular calcification and atheromatous calcification of either the MCA (M1 segment) or ICA (extra- and intracranial parts). Conclusions: Our study implies that intracranial microvascular calcification is highly prevalent in elderly populations. Additionally, we discovered significant correlation between microvascular calcification and that of the media in mascrovasculature, suggesting a causal link between medial sclerosis and dysfunction of the neurovascular unit.
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