While it has been widely confirmed that cerebral blood flow is closely coupled with brain metabolism, it remains a matter of controversy whether capillary flow is directly controlled to meet the energy demands of the parenchyma. Since the capillary is known to lack smooth muscle cells, it has generally been considered that capillary flow is not regulated in situ. However, we now have increasing data supporting the physiological control of capillary flow. The observation of heterogeneity in the microcirculation in vivo has suggested that intravascular factors may be involved in the flow control, including non-Newtonian rheology, red blood cell flow, leukocyte adhesion, release of vasoactive mediators, and expression of glycoproteins on the endothelial cells. Astrocytes, a key mediator of the neurovascular unit, and intrinsic innervation may also regulate capillary flow. In addition, recent findings on pericyte contractility have attracted the attention of many researchers. Finally, based on these findings, we present a new model of flow control, the proximal integration model, in which localized neural activity is detected at nearby capillaries and the vasodilation signal is transmitted proximally along the vessel. Signals are then integrated at the precapillary arterioles and other arterioles further upstream and regulate the capillary flow.
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