The Role of Pericytes in Neurovascular Unit Remodeling in Brain Disorders

Abstract

Neurons are extremely vulnerable cells that tightly rely on the brain’s highly dynamic and complex vascular network that assures an accurate and adequate distribution of nutrients and oxygen. The neurovascular unit (NVU) couples neuronal activity to vascular function, controls brain homeostasis, and maintains an optimal brain microenvironment adequate for neuronal survival by adjusting blood-brain barrier (BBB) parameters based on brain needs. The NVU is a heterogeneous structure constituted by different cell types that includes pericytes. Pericytes are localized at the abluminal side of brain microvessels and contribute to NVU function. Pericytes play essential roles in the development and maturation of the neurovascular system during embryogenesis and stability during adulthood. Initially, pericytes were described as contractile cells involved in controlling neurovascular tone. However, recent reports have shown that pericytes dynamically respond to stress induced by injury upon brain diseases, by chemically and physically communicating with neighboring cells, by their immune properties and by their potential pluripotent nature within the neurovascular niche. As such, in this paper, we would like to review the role of pericytes in NVU remodeling, and their potential as targets for NVU repair strategies and consequently neuroprotection in two pathophysiologically distinct brain disorders: ischemic stroke and Alzheimer’s disease (AD).

Pericytes in Brain Injury and Repair After Ischemic Stroke

“…Pericytes and ECs are continuously separated by basal lamina. However, the basal lamina between pericytes and ECs have some hole-like structures, which allow EC-pericyte communication and interaction in a peg-socket manner [21]. Adhesion and gap junctions are found in the peg-socket contacts between ECs and pericytes.…”

Common Mechanisms of Alzheimer's Disease and Ischemic Stroke: The Role of Protein Kinase C in the Progression of Age-Related Neurodegeneration

“…PKC remodeling of the neurovascular unit has been proposed as a mechanism by which blood-born products enter and accumulate within the brain [141]. Pericytes, astrocytes, and endothelial cells can become damaged during stroke onset and AD progression [142].…”

Vascular Remodelling is Impaired in Parkinson Disease

“…Due to tissue availability we only evaluated the changes in the MFG, in which the pericytes changes were similar to that of endothelial cells [1]. The interactions between endothelial cell and pericytes on vascular remodelling are well documented [18][19][20]. For example, pericytes can regulate the proliferation and survival of endothelial cells and endothelial cells mediate the recruitment of pericytes [21].…”