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.

Keywords: Cerebrovascular plasticity; blood–brain barrier; brain microvascular endothelial cells; cerebrovascular architecture; neurovascular coupling.

Figure 1.

Cerebrovascular architecture displays profound plasticity during the human lifespan. A summary of changes during: (a) development, (b) homeostasis, and (c) aging, injury, and disease. (d) Microvascular density increases via angiogenesis in the brain. Shown is the mouse postnatal cortex, arrowheads denote endothelial sprouts. (e) The blood–brain barrier (BBB) displays functionally low permeability during early stages of brain development; here, a guinea pig embryo injected with trypan blue demonstrates restriction of dye entry into CNS. (f) Neurovascular coupling is the process by which increases in neural activity create changes in local cerebral blood flow and cerebral consumption of oxygen; here, we display a change in local total hemoglobin concentration (dark red) in response to electrical stimulation in the somatosensory cortical surface of a rat. (g) Chronic hypoxia results in increased microvascular density in the mouse motor cortex. (h) TBI results in a rapid decrease in microvascular density in rats. (i) During Alzheimer’s disease, the most common neurodegenerative disease, amyloid-beta accumulates around human microvessels and BBB integrity is compromised (downregulation of the tight junction protein claudin-5) among other cerebrovascular changes. Images were cropped from original and have labels added. Source: Figure 1(d) is reproduced with permission from Walchli et al.; Figure 1(e) is reproduced with permission from Saunders et al.; Figure 1(f) is reproduced with permission from Chen et al.; Figure 1(g) is reproduced with permission from Boero et al.; Figure 1(h) is reproduced with permission from Obenaus et al.; and Figure 1(i) is reproduced with permission from Keaney et al.

Figure 2.

Cerebrovascular architecture. (a) Arterial architecture: (i) inferior view of the base of the brain with cerebral arterial Circle of Willis; (ii) magnified view of the Circle of Willis; and (iii) right lateral view of the right hemisphere. (b) Microvasculature ultrastructure in the cerebral cortex: (i) schematic illustration of the vasculature in the cerebral cortex showing both arterial and venous systems. Pial arteries located on the surface penetrate deep into the cerebral cortex as penetrating arterioles, which branch into capillary beds that then reemerge from the cortex as ascending venules. (ii) Scanning electron micrograph of a corrosion cast showing the vasculature of the temporal lobe of the human cerebral cortex. (Scale bar = 375 µm): (1) pial artery, (2) long cortical artery, (3) middle cortical artery, (4) short cortical artery, (5) cortical vein, (6) subpial zone, (7) precapillary vessel with blind ending, (8) superficial capillary zone, (9) middle capillary zone, and (10) deep capillary zone. (c) Neurovascular unit. (i) Schematic illustration of the neurovascular unit comprised of brain microvascular endothelial cells surrounded by pericytes and astrocytes. (ii) Electron microscope cross section of a capillary from the rat frontoparietal cortex. BM: basement membrane; BMECs: brain microvascular endothelial cells; TJ: tight junction. Source: Figure 2(b)(i) is reproduced with permission from Chen et al.; Figure 2(b)(ii) is reproduced with permission from Reina-De La Torre et al.; Figure 2(c)(i) is reproduced with permission from Walchli et al.; and Figure 2(c)(ii) is reproduced with permission from Farkas & Luiten.