Rodent Models of Cerebral Microinfarct and Microhemorrhage.

Abstract

Microinfarcts are prevalent but tiny ischemic lesions that may contribute to vascular cognitive impairment and dementia (Figure 1A and 1B).1 They are defined as areas of tissue infarction, often with gliosis or cavitation, visible only by examination of the autopsied brain at a microscopic level.2,3 Numerous autopsy studies have now shown that a greater microinfarct burden is correlated with increased likelihood of cognitive impairment.2,3 Cerebral microinfarcts are observed postmortem in the brains of ≈43% of patients with Alzheimer’s disease, 62% of patients with vascular dementia, and 24% of nondemented elderly subjects.4 However, reported microinfarct numbers are a significant underestimation of total burden, as only a small portion of the brain is examined at routine autopsy.1 Indeed, they can number in the hundreds to thousands within a single brain. Microinfarcts can arise from a variety of etiologies, including cerebral small vessel disease, large vessel disease, cerebral hypoperfusion, and cardiac disease, but their role in the pathogenesis of vascular cognitive impairment and dementia remains poorly understood.3,5–7 Figure 1. Human microinfarcts and microhemorrhages in cerebral amyloid angiopathy (CAA) cases. A , A cortical microinfarct on a hematoxylin & eosin–stained section. B , Microinfarct (black arrow) on a T2-weighted ex vivo magnetic resonance imaging (MRI) scan. C , A cortical microhemorrhage on a hematoxylin & eosin–stained section. D , Multiple lobar microbleeds (white arrows) on a gradient-repeat echo ex vivo MRI scan. Microhemorrhages are microscopic bleeds caused by rupture of cerebral microvessels, generating lesions on a similar scale as microinfarcts (Figure 1C and 1D).5 Pathologically, old microhemorrhages are defined as focal depositions of iron-positive hemosiderin-containing macrophages. Unlike microinfarcts, microhemorrhages easily escape detection on neuropathological examination, suggesting that they are not as widespread as microinfarcts. However, they can be detected …