Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

Abstract

Vessel loss in the aging brain is commonly reported, yet important questions remain concerning whether there are regional vulnerabilities and what mechanisms could account for these regional differences, if they exist. Here we imaged and quantified vessel length, tortuosity and width in 15 brain regions in young adult and aged mice. Our data indicate that vessel loss was most pronounced in white matter followed by cortical, then subcortical grey matter regions, while some regions (visual cortex, amygdala, thalamus) showed no decline with aging. Regions supplied by the anterior cerebral artery were more vulnerable to loss than those supplied by middle or posterior cerebral arteries. Vessel width and tortuosity generally increased with age but neither reliably predicted regional vessel loss. Since capillaries are naturally prone to plugging and prolonged obstructions often lead to vessel pruning, we hypothesized that regional susceptibilities to plugging could help predict vessel loss. By mapping the distribution of microsphere-induced capillary obstructions, we discovered that regions with a higher density of persistent obstructions were more likely to show vessel loss with aging and vice versa. These findings indicate that age-related vessel loss is region specific and can be explained, at least partially, by regional susceptibilities to capillary plugging.

SARS-CoV-2 binding to ACE2 triggers pericyte-mediated angiotensin-evoked cerebral capillary constriction

“…On the other hand, the fact that blood contains cells results in its viscosity increasing dramatically at small diameters 35 , so that even small pericyte-mediated constrictions can have a large effect. Indeed, complete stalling of blood flow in capillaries can occur as a result of neutrophils (which are less distensible than red blood cells) becoming stuck at narrow parts of the vessel, for example near constricted pericytes [36][37][38] , and this could also transform a small constriction into a much larger reduction of blood flow.…”

Increased capillary stalling is associated with endothelial glycocalyx loss in subcortical vascular dementia

“…Recent studies have revealed the significance of capillary stalling in aging, stroke, Alzheimer's disease, polycythemia and thrombocythemia 3,4,5,6,11,21,22,23 . In fact, capillary stalling largely impacts on CBF, and cognitive functions can be improved by suppressing capillary stalling in Alzheimer's disease 6,24 .…”

Cerebral blood flow decrease as an early pathological mechanism in Alzheimer's disease

“…It will be important to reproduce these results in human AD patients. In wild-type mice, capillary block increases with ageing and can lead to vessels being pruned [ 159 ]. Remarkably, although modelling suggested that the increased block in AD would lead to a decrease of CBF of less than 5%, applying intraperitoneally a high concentration of an antibody to a neutrophil surface marker (Ly6G) led to a relief of capillary block, an increase of blood flow by 26–32% and improved memory.…”