Pericytes in Brain Injury and Repair After Ischemic Stroke

Abstract

Pericytes are functional components of the neurovascular unit (NVU). They provide support to other NVU components and maintain normal physiological functions of the blood-brain barrier (BBB). The brain ischemia and reperfusion result in pathological alterations in pericytes. The intimate anatomical and functional interactions between pericytes and other NVU components play pivotal roles in the progression of stroke pathology. In this review, we depict the biology and functions of pericytes in the normal brain and discuss their effects in brain injury and repair after ischemia/reperfusion. Since ischemic stroke occurs mostly in elderly people, we also review age-related changes in pericytes and how these changes predispose aged brains to ischemic/reperfusion injury. Strategies targeting pericyte responses after ischemia and reperfusion may provide new therapies for ischemic stroke.

Keywords: Blood-brain barrier; Ischemic stroke; Neurovascular unit; Pericyte.

Figure 1. Pericyte classification based on its location, morphology and protein expression

Arterial pericytes are located at the arteriole end of the capillary bed. These pericytes have many circumferential processes to surround capillaries and express high levels of α-smooth muscle actin (α-SMA). Capillary pericytes reside in the middle of the capillary bed. They give out more longitudinal processes and express less α-SMA. Venule pericytes are located at the venule end of the capillary. This subtype of pericytes has a stellate morphology and modulates the infiltration of peripheral immune cells into brain paranchyma.

Figure 2. Interactions between pericyte and other neurovascular unit (NVU) components

As a main component of NVU, pericytes not only exert barrier function by themselves but also promote physiological functions of other BBB components, including endothelial cells, basal lamina, astrocytes and neurons.

Figure 3. Pericyte-derived angiogenic factors and related signaling pathways after ischemic stroke

During ischemia, several signaling pathways are activated and each of them is involved in various steps in angiogenesis. VEGF binds to its receptor on pericytes and endothelial cells and results in proliferation of these cells. Besides, hypoxia and VEGF signaling induce up-regulation of Ang2 expression in endothelial cells and up-regulation of Ang1/Tie2 (Ang1 receptor) in pericytes, which all mediate further proliferation of endothelial cells and pericytes and the following vascular formation. PDGFR-β is found to be induced specifically in peri-infarct pericytes. Meanwhile, peri-infarct endothelial cells could produce more PDGF-β. Activation of PDGFR-β by PDGF-β in pericytes is found to be indispensable for migration of pericytes to the newly formed endothelial tubes, which is a vital step for neovasculation. RG5 is important for pericyte maturation. EC, endothelial cells; PC, pericyte; PDGF: platelet-derived growth factor; PDGFR: PDGF receptor; VEGF: Vascular endothelial growth factor; VEGFR: VEGF receptor;