Cerebral microvascular pericytes and neurogliovascular signaling in health and disease

• Communication between the elements of NVU is needed for neurovascular coupling.
• Pericytes contribute to regulation of the microvascular blood flow and BBB integrity.
• Pericyte–endothelia communication controls vasculogenesis and leukocyte infiltration.
• Pericyte dysfunction may contribute to impaired reperfusion, diabetic retinopathy, and dementia.
• Microvascular protection is essential for successful neuroprotection.

Increases in neuronal activity cause an enhanced blood flow to the active brain area. This neurovascular coupling is regulated by multiple mechanisms: Adenosine and lactate produced as metabolic end-products couple activity with flow by inducing vasodilation. As a specific mechanism to the brain, synaptic activity-induced Ca2+ increases in astrocytes, interneurons and neurons translate neuronal activity to vasoactive signals such as arachidonic acid metabolites and NO. K+ released onto smooth muscle cells through Ca2+-activated K+ channels on end-feet can also induce vasodilation during neuronal activity. An intense communication between the endothelia, pericytes and astrocytes is required for development and functioning of the neurovascular unit as well as the BBB. The ratio of pericytes to endothelial cells is higher in the cerebral microcirculation than other tissues. Pericytes play a role in distribution of microvascular blood flow in response to the local demand as a final regulatory step after arterioles, which feed a larger cohort of cells. Pericyte–endothelial communication is essential for vasculogenesis. Pericyte also take part in leukocyte infiltration and immune responses. The microvascular injury induced by ischemia/reperfusion plays a critical role in tissue survival after recanalization by inducing sustained pericyte contraction and microcirculatory clogging (no-reflow) and by disrupting BBB integrity. Suppression of oxidative/nitrative stress or sustained adenosine delivery during re-opening of an occluded artery improves the outcome of recanalization by promoting microcirculatory reflow. Pericyte dysfunction in retinal microvessels is the main cause of diabetic retinopathy. Recent findings suggest that the age-related microvascular dysfunction may initiate the neurodegenerative changes seen Alzheimer׳s dementia.This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.