The Interplay Between Brain Vascular Calcification and Microglia

Abstract

Vascular calcifications are characterized by the ectopic deposition of calcium and phosphate in the vascular lumen or wall. They are a common finding in computed tomography scans or during autopsy and are often directly related to a pathological condition. While the pathogenesis and functional consequences of vascular calcifications have been intensively studied in some peripheral organs, vascular calcification, and its pathogenesis in the central nervous system is poorly characterized and understood. Here, we review the occurrence of vessel calcifications in the brain in the context of aging and various brain diseases. We discuss the pathomechanism of brain vascular calcification in primary familial brain calcification as an example of brain vessel calcification. A particular focus is the response of microglia to the vessel calcification in the brain and their role in the clearance of calcifications.

Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study

“…63 These occur as the aging process causes loss of elasticity and gradual stiffening of the vessel walls from inflammation, calcification, etc. 64 Aging contributes to diminished cerebral capillary density, distortion of the microvascular wall, smooth muscle degeneration in the vessel walls, endothelial dysfunction, elevated cerebral blood flow velocity (CBFV) pulsatility, elevated microvascular resistance, etc. 63,[65][66][67][68][69] Aging also causes cardiovascular changes where diastolic CBFV is reduced more than systolic causing augmented pulsatility which in turn can cause increase in cerebral vascular resistance and remodeling of the vessels leading to eventual microcirculatory damage and small vessel disease.…”

Heterozygous NOTCH1 Variants Cause CNS Immune Activation and Microangiopathy

“…The prevalent view is that medial calcification is related to phenotypic changes of smooth muscle cells and pericytes into cells that promote mineralization, resulting in a calcifying microangiopathy. Inflammatory cytokines are known to stimulate such phenotypic changes, 20 suggesting that AGS and NOTCH1 ‐related disease share this mechanism. However, it is possible that NOTCH1 ‐related vascular calcifications are mediated in different ways or are multifactorial, inflammation being one factor.…”

Case report: Thrombolysis in patients with acute ischemic stroke and cerebral cavernous malformation

“…Researchers have associated calcification in CCM with recurrent thrombosis ( 27 ). Furthermore, alterations in the composition and degeneration of the basement membrane have been described in calcific vasculature, with astrocytes around calcifications showing positivity for 2-ω-carboxyethylpyrrole, indicative of inflammation and oxidative stress ( 28 ). Such alterations in calcification exacerbate inter-brain endothelial junctions.…”