Distinct neuroinflammatory patterns between cerebral microbleeds and microinfarcts in cerebral amyloid angiopathy

Abstract

In this neuropathological study, we investigated neuroinflammation surrounding recent and old cerebral microbleeds (CMBs) and cerebral microinfarcts (CMIs) in 18 cases of cerebral amyloid angiopathy (CAA). We used several serial stainings and immunolabellings to identify microvascular lesions, define their recent or old stage, and characterize neuroinflammatory response (scavenging activity and astrogliosis). We found that both CMBs and CMIs induce a neuroinflammatory response, which was more pronounced in old lesion than recent. Astrogliosis and scavenging activity were differentially prominent according to the ischemic/hemorrhagic nature of the lesion. Our findings provide insights into the pathophysiology of microvascular injuries in CAA.

Figure 1

Neuroinflammatory pattern of recent cerebral microbleeds (CMBs) and recent microinfarcts (CMIs). The left panel shows a neuropathological illustration of a recent CMI and a recent CMB. From top to bottom, we show the Perl's staining (used to assess the recent or old stage), GFAP (activated astrocytes in brown), and CD163 (activated microglia and macrophages in brown) immunolabelings. The recent CMIs appeared as a circumscribed lesion characterized by a myelin loss (tissue pallor). The recent CMBs was characterized by an extravasation of fresh red blood cells with few iron deposition. These microvascular lesions presented a distinct inflammatory pattern according to their nature: recent CMIs exhibited more activated microglia and macrophages (cells with scavenging activity) than recent CMBs while activated astrocytes tended to be more abundant in recent CMBs than recent CMIs (see the right panel for statistical analysis). Scale bars = 100 μm. (**P < 0.001).

Figure 2

Neuroinflammatory pattern of old cerebral microbleeds (CMBs) and old cerebral microinfarcts (CMIs). The left panel shows a neuropathological illustration of an old CMI and an old CMB. From top to bottom, we show the Perl's staining (used to assess the recent or old stage), GFAP (activated astrocytes, in brown), and CD163 (activated microglia and macrophages, in brown) immunolabelings. Old CMIs were characterized by tissue loss, cavitation and gliosis and without iron deposition while old CMBs exhibit an abundant amount of iron deposition in the vicinity of an abnormal small vessel. Again, we observed a distinct inflammatory pattern according to the ischemic/hemorrhagic nature of the lesions: the astrogliosis reaction was higher in old CMIs than in old CMBs while the expression of cells with scavenging activity (activated microglia and macrophages) was more important in old CMBs (see the right panel for statistical analysis). Scale bars = 100 μm. ((*P < 0.005, **P < 0.001)