Figure 10.

Occasionally microbleeds (arrows) in cerebral cortex may be visible already during brain cutting (A). An accumulation of hemosiderin around a cortical arteriole stains strongly positively for iron (B). The breached BBB at the microbleed leaks plasma fibrinogen (brown; C). The wall of a cortical arteriole (D) is markedly thinner than that of a WM arteriole (E; blue bars in D vs. E), while their outer diameters (red bars) are of approximately the same magnitude. This is a likely explanation for the predominant location of microbleeds in cortical and deep GM. The thick wall of a WM arteriole from a CADASIL patient at a quiescent stage of the disease has not allowed virtually any leakage of fibrinogen (E). Extravasated fibrinogen is normally taken up by Purkinje cells (PCs) from cerebrospinal fluid 51. Thus, negative fibrinogen staining of cerebellar PCs (arrows; F) verifies that significant leakage has not occurred in this patient at a quiescent stage, whereas in another CADASIL patient, who had suffered an infarct just before death, PCs (arrows) are strongly immunopositive for fibrinogen reflecting the breakdown of BBB (G).