Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy

Capillary perfusion in the brain is characterized by an essentially continuous flow of erythrocytes and plasma in almost all capillaries. Rapid fluctuations and spatial heterogeneity or red blood cell (RBC) velocity (0.5-1.8 mm/s) within the capillary network are present. In addition, low-frequency (4-8 cpm) synchronous oscillations in RBC velocity in the capillary network emerge when perfusion to cerebral tissue is challenged. Despite the tortuous, three-dimensional architecture of microvessels, functional intercapillary anastomoses are absent. At rest, red cells travel through the capillary network in 100-300 ms along 150- to 500-micron-long paths. Physiological challenges elicit sizable changes in RBC velocity with a minor role for capillary recruitment, change in capillary diameter, or flow shunting. During acute hypoxia, RBC velocity increases in all capillaries; the corresponding response to hypereapnia is more complex and involves redistribution of capillary flow toward more homogeneous perfusion. The response of capillary flow to decreased perfusion pressure reflects autoregulation of cerebral blood flow but also involves intranetwork redistribution of RBC flow between two populations of capillaries, postulated as thoroughfare channels and exchange capillaries. Flow reserve may be provided by the thoroughfare channels and may help maintain flow velocity and capillary exchange and protect the microcirculation from perfusion failure. Isovolemic hemodilution increases RBC velocity three- to fourfold and increases RBC flux to a moderate degree with a relatively small decrease in capillary hematocrit, under normal and compromised arterial blood supply. In cerebral ischemia, leukocyte adhesion is enhanced and appears reversible when the ischemia is moderate but may be progressive when the injury is severe. The observed flow behavior suggests the presence of a physiological regulatory mechanism of cerebral capillary flow that may involve communication among various microvascular and parenchymal cells and utilize locally acting endothelial and parenchymal mediators such as endothelium-derived relaxing factor or nitric oxide.