Pericyte-glial cell interactions: Insights into brain health and disease

Abstract

Pericytes are multi-functional mural cells of the central nervous system that cover the capillary endothelial cells. Pericytes play a vital role in nervous system development, significantly influencing the formation, maturation, and maintenance of the central nervous system. An expanding body of studies has revealed that pericytes establish carefully regulated interactions with oligodendrocytes, microglia, and astrocytes. These communications govern numerous critical brain processes, including angiogenesis, neurovascular unit homeostasis, blood-brain barrier integrity, cerebral blood flow regulation, and immune response initiation. Glial cells and pericytes participate in dynamic and reciprocal interactions, with each influencing and adjusting the functionality of the other. Pericytes have the ability to control astrocyte polarization, trigger differentiation of oligodendrocyte precursor cells, and initiate immunological responses in microglia. Various neurological disorders that compromise the integrity of the blood-brain barrier can disrupt these communications, impair waste clearance, and hinder cerebral blood circulation, contributing to neuroinflammation. In the context of neurodegeneration, these disruptions exacerbate pathological processes, such as neuronal damage, synaptic dysfunction, and impaired tissue repair. This article explores the complex interactions between pericytes and various glial cells in both healthy and pathological states of the central nervous system. It highlights their essential roles in neurovascular function and disease progression, providing important insights that may enhance our understanding of the molecular mechanisms underlying these interactions and guide potential therapeutic strategies for neurodegenerative disorders in future research.

Keywords: brain; inflammation; neuroprotection; neurovascular function; therapeutic targets.

Figure 1

Neurovascular unit composition and structure. This image depicts the neurovascular unit, emphasizing its key cellular components and their interactions in maintaining brain homeostasis. Central to the unit are the capillaries, formed by endothelial cells that establish the blood-brain barrier. Pericytes encircle the endothelial cells, regulating vascular stability and permeability, while astrocytes extend their end-feet to envelop capillaries, providing metabolic support and reinforcing barrier integrity. Microglia monitor the environment and interact with other neurovascular unit cells to respond to pathological changes. Oligodendrocytes, responsible for myelin formation, support neuronal energy demands and indirectly interact with the vascular system. Created with BioRender.com.

Figure 2

Pericyte-astrocyte interactions in physiological and pathological states. The illustration highlights their roles in regulating cerebral blood flow, maintaining BBB integrity, and facilitating neurovascular signaling. Key molecules, including AQP4, Cx30 and Cx43, PGE2, and PDGFRβ, mediate communication and support vascular and neural homeostasis. Dysregulation of these interactions is implicated in cerebrovascular and neurodegenerative disorders. Created with BioRender.com. AQP4: Aquaporin 4; BBB: blood–brain barrier; CBF: cerebral blood flow; Cx30: connexin 30; Cx43: connexin 43; PDGFRβ: platelet-derived growth factor receptor beta; PGE2: prostaglandin E2.

Figure 3

Pericyte-oligodendrocyte interactions in physiological and pathological states. This figure illustrates the key interactions between pericytes and oligodendrocytes, mediated by survival factors and laminin subunit alpha 2, which play critical roles in promoting oligodendrocyte precursor cell differentiation and supporting neural health. Created with BioRender.com.

Figure 4

Pericyte-microglia interactions in healthy and pathological states. This figure illustrates the dynamic interactions between pericytes and microglia under physiological and pathological conditions. In healthy states, pericytes and microglia collaborate to maintain blood–brain barrier integrity, regulate neurovascular unit function, and support immune surveillance. In pathological states, these interactions are disrupted, leading to the clustering of microglia around capillaries and altered pericyte morphology. Inflammatory mediators provoke these pathological changes, emphasizing the role of inflammation in modulating pericyte and microglia dynamics in neurological disorders. Created with BioRender.com. CBF: Cerebral blood flow; IBA1: ionized calcium-binding adapter molecule 1; PDGFR: platelet-derived growth factor receptor.