Genetic determinants of insufficiency of the collateral circulation

It has been estimated that approximately two million neurons, sixteen billion synapses and twelve kilometers of axons are lost each minute following anterior large-vessel stroke. The level of collateral blood flow has become recognized as a primary determinant of the pace of this loss and an important factor in clinical decision-making. Many of the topics in this review cover recent developments that have not been reviewed elsewhere. These include that: the number and diameter of collaterals and collateral blood flow vary greatly in the brain and other tissues of healthy individuals; a large percentage of individuals are deficient in collaterals; the underlying mechanism arises primarily from naturally occurring polymorphisms in genes/genetic loci within the pathway that drives collateral formation during development; evidence indicates collateral abundance does not exhibit sexual dimorphism; and that collaterals—besides their function as endogenous bypass vessels—may have a physiological role in optimizing oxygen delivery. Animal and human studies in brain and other tissues, where available, are reviewed. Details of many of the studies are provided so that the strength of the findings and conclusions can be assessed without consulting the original literature. Key questions that remain unanswered and strategies to address them are also discussed.