Cerebral microbleeds in the elderly: a pathological analysis

Abstract

Background and purpose: Cerebral microbleeds in the elderly are routinely identified by brain MRI. The purpose of this study was to better characterize the pathological basis of microbleeds.

Methods: We studied postmortem brain specimens of 33 individuals with no clinical history of stroke and with an age range of 71 to 105 years. Cerebral microbleeds were identified by presence of hemosiderin (iron), identified by routine histochemistry and Prussian blue stain. Cellular localization of iron (in macrophages and pericytes) was studied by immunohistochemistry for smooth muscle actin, CD68, and, in selected cases, electron microscopy. Presence of β-amyloid was analyzed using immunohistochemistry for epitope 6E10.

Results: Cerebral microbleeds were present in 22 cases and occurred at capillary, small artery, and arteriolar levels. Presence of microbleeds occurred independent of amyloid deposition at site of microbleeds. Although most subjects had hypertension, microbleeds were present with and without hypertension. Putamen was the site of microbleeds in all but 1 case; 1 microbleed was in subcortical white matter of occipital lobe. Most capillary microbleeds involved macrophages, but the 2 microbleeds studied by electron microscopy demonstrated pericyte involvement.

Conclusions: These findings indicate that cerebral microbleeds are common in elderly brain and can occur at the capillary level.

Figure 1

Occipital lobe, subcortical white matter. A: Capillary with hemosiderin; H&E, Prussian blue. (Original magnification X520) B, C: Capillary with hemosiderin; H&E, Prussian blue. (Original magnification X520) D: Alpha smooth muscle actin immunostain of capillary. Immunoreactivity is adjacent to ablumenal surface of endothelium, where pericytes are located. (Original magnification X520)

Figure 2

Electron microscopy of capillary in subcortical white matter, stained for iron (Prussian blue). Pericyte, attached to capillary wall and surrounded by basement membrane, contains dense deposits of iron. Tight junction of endothelial cell (red arrows) is immediately adjacent to pericyte. Also shown are basal lamina (green arrow), endothelium (blue arrow), hemosiderin in pericyte (white asterisk), red blood cell (yellow #), and blood vessel lumen (red arrowhead). (Original magnification X15,000)

Figure 3

Pericapillary deposition of hemosiderin (brown) within macrophage (red) in putamen, using CD68 immunostain. (Original magnification X600)

Figure 4

Proposed mechanism for extravasation of red blood cells from brain capillaries. Opening of tight junction allows for pericyte erythrophagocytosis, with adjacent macrophage available as alternative or secondary site for phagocytosis.