Role of Pericytes in Neurovascular Unit and Stroke

Abstract

The concept of the neurovascular unit (NVU) has shifted the focus of stroke research from neuron-centric views to the microvasculature. We now realize that a successful neuroprotection is not feasible without microvascular protection. Recent studies on pericytes, long-neglected cells of the NVU have provided insight into the regulation of microcirculatory flow, blood–brain barrier (BBB) maintenance and angiogenesis. Ischemia induces persistent pericyte contraction that does not recover after recanalization, causing incomplete reflow in microcirculation. Supporting this, clinical imaging studies show that tissue reperfusion is not always obtained after recanalization and that increased capillary transit time heterogeneity (a measure of incomplete reperfusion) is a good predictor of the tissue destined to infarct. Ischemia-induced pericyte dysfunction and death may also contribute to post-ischemic BBB leakiness as suggested by findings in CADASIL transgenic mice and diabetic retinopathy. Therefore, prevention of pericyte dysfunction may improve the outcome of recanalization therapies by promoting microcirculatory reperfusion and preventing hemorrhage and edema. Indeed, suppression of oxidative/nitrative stress or sustained adenosine delivery during recanalization has been shown to improve the stroke outcome by promoting microcirculatory reflow and restoring BBB integrity. In the peri-infarct tissue, pericytes are detached from microvessels and contribute to angiogenesis and neurogenesis, hence, stimulation of this process appears as a novel target for post-stroke recovery.