Cerebral microbleeds: Beyond the macroscope

Abstract

While being increasingly recognized in clinical routine, brain microbleeds remain a puzzling finding for physicians. These small dot-like lesions are thought to be old perivascular collections of hemosiderin deposits. They can be found in different neurological settings such as cerebrovascular or neurodegenerative diseases. While their microscopic size would suggest considering these lesions as anecdotal, they are now regarded as biomarkers of severity of an underlying cerebrovascular disease. Their natural history and the interactions with surrounding brain cells remain unknown. However, their presence may impact therapeutic decisions. Deciphering the biological mechanisms leading to, or following microbleeds would enable us to address a key question: do microbleeds arise and impact the surrounding parenchyma like a miniature version of intracerebral hemorrhages or do they represent a different kind of injury? We hereby discuss, based on both clinical and experimental literature, the gap between the definition of microbleeds coming from neuroimaging and the pathophysiological hypotheses raised from histopathological and experimental data. Our analysis supports the need for a convergent effort from clinicians and basic scientists to go beyond the current “macro” view and disclose the cellular and molecular insights of these cerebral hemorrhagic microlesions.

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds

“…Here, overall prevalence of CMB was 45%, higher than previous IS cohorts, 9 , 43 and equivalent to IS and ICH mixed stroke cohorts. 43 The current study included about 20% of subjects with a history of ICH.…”

“… 10 Experimental models for CMB include mice subcutaneously injected with lipopolysaccharide. 9 , 11 CMB are known to be induced by infective endocarditis 12 or bacterial sepsis. 6 …”

The severity of microstrokes depends on local vascular topology and baseline perfusion

“…In recent decades it has become evident that microinfarcts are linked to various pathologies, e.g. cerebral amyloid angiopathy (CAA), cognitive impairment, Alzheimer's disease (AD) and dementia [6][7][8][9][10]. For example, postmortem neuropathological studies revealed that 62% of patients with vascular dementia also suffered from cortical microinfarcts [11].…”

“…Moreover, the estimated total number of microinfarcts per individual can be as high as several thousand [12,13]. Microinfarcts can either be ischemic (microstroke) or hemorrhagic (microhaemorrhage, cerebral microbleed) [7][8][9]14]. The size of the resulting tissue lesion is comparable for microstrokes and microhaemorrhages [7].…”

GJA1 Gene Polymorphisms and Topographic Distribution of Cranial MRI Lesions in Cerebral Small Vessel Disease

“…Breakdown of the BBB causes leakage of plasma substances, while chronic hypoperfusion inhibits the generation and repair of myelin, thereby injuring the axon and causing WMH. CMB are caused by BBB breakdown or amyloid β (Aβ) deposition during cerebral amyloid angiopathy (CAA) (3,33). Our findings suggest that GJA1 gene SNPs are mainly associated with EC pathways or Aβ deposition.…”