Blood Flow in the Cerebral Capillary Network: A Review Emphasizing Observations with Intravital Microscopy

Abstract

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.

Comparison of gradient- and spin-echo imaging: CBF, CBV, and MTT measurements by bolus tracking

“…This corresponds to an increase in volume of the capillaries of [(5.91/ 2) 2 Ϫ (4.29/2) 2 ]/(4.29/2) 2 ϭ 90%. The lack of recruitment is also in good agreement with earlier findings (15).…”

Two-photon imaging of capillary blood flow in olfactory bulb glomeruli

“…Our values are compatible with those reported for capillaries at the cortical surface (for review, see ref. 35) and further in depth when observed with confocal (36, 37) or two-photon laser scanning microscopy (12). In the olfactory bulb, we determined that neither the mean values nor the instantaneous values of RBC velocity and linear density were correlated.…”

Can Restoring Incomplete Microcirculatory Reperfusion Improve Stroke Outcome after Thrombolysis?

“…Doppler shifts created by erythrocytes bypassing through patent capillaries and arteriolo-veneous anastomoses or thoroughfare channels may have led to pseudonormalized signal after recanalization. 75 Therefore, labeling erythrocytes might be a more reasonable approach to study the microcirculatory occlusions in vivo as well as ex vivo (Figure 1). In conclusion, it appears that the resistance increase in some capillaries because of intraluminal cell aggregates, which aggravates capillary flow heterogeneity and reduces oxygenation, 76,77 may not be reliably assessed by some cerebral blood flow detection methods depending on experimental factors such as the tracer used, circulation time of the tracer, sampling of region of interests, and tissue processing protocols.…”