Cerebrovascular plasticity: Processes that lead to changes in the architecture of brain microvessels

Abstract

The metabolic demands of the brain are met by oxygen and glucose, supplied by a complex hierarchical network of microvessels (arterioles, capillaries, and venules). Transient changes in neural activity are accommodated by local dilation of arterioles or capillaries to increase cerebral blood flow and hence nutrient availability. Transport and communication between the circulation and the brain is regulated by the brain microvascular endothelial cells that form the blood–brain barrier. Under homeostatic conditions, there is very little turnover in brain microvascular endothelial cells, and the cerebrovascular architecture is largely static. However, changes in the brain microenvironment, due to environmental factors, disease, or trauma, can result in additive or subtractive changes in cerebrovascular architecture. Additions occur by angiogenesis or vasculogenesis, whereas subtractions occur by vascular pruning, injury, or endothelial cell death. Here we review the various processes that lead to changes in the cerebrovascular architecture, including sustained changes in the brain microenvironment, development and aging, and injury, disease, and repair.

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

“…While developmental brain angiogenesis occurs simultaneously with BBB formation [35], during adulthood brain angiogenesis is typically associated with BBB breakdown [36][37][38]. Here we observed that both microvessels and capillaries restricted transport of 500 kDa dextran indicating the presence of a confluent endothelium with preserved barrier function (Fig.…”

“…The culmination of brain angiogenesis during development results in a hierarchical BBB with profound heterogeneity in structure and phenotype [38,41,42]. However, after development, angiogenesis is generally restricted to pathological conditions which alter BBB structure and phenotype [36][37][38]. Here we developed an in vitro model of brain angiogenesis using iPSC-derived BMECs (dhBMECs) to study brain angiogenesis.…”

Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

“…The culmination of brain angiogenesis during development results in a hierarchical BBB with profound heterogeneity in structure and phenotype [35][36][37]. However, after development, angiogenesis is generally restricted to pathological conditions which alter BBB structure and phenotype [37][38][39]. Here we develop an in vitro model of brain angiogenesis using iPSC-derived BMECs (dhBMECs) to study developmental and pathological angiogenesis.…”

“…Under homeostatic conditions angiogenesis is not prevalent in the adult brain; however, brain angiogenesis is associated with pathological conditions, including neurodegenerative disease, brain cancer, and stroke [37]. Production of reactive oxygen species (ROS) is associated with these conditions and may contribute to BBB disruption and pathological angiogenesis [60].…”

“…Future work is required to examine how iPSC-derived pericytes and other cells of the BBB may alter angiogenesis in vitro. 2The stability of angiogenic vessels is not addressed: the adult cerebrovasculature is highly stable, with limited angiogenesis [37]. For example, over 30 days changes in capillary length, diameter or branching were not observed in the adult mouse somatosensory and motor cortex [68].…”