Endothelialglial

Endothelialglial refers to the integrated functional relationship between brain microvascular endothelial cells and glial cells, particularly astrocytes, within the cerebral vasculature. It is not a distinct cell type but a concept used to emphasize the coordinated activities that maintain the blood-brain barrier (BBB) and the health of the neurovascular unit. The idea highlights how endothelial and glial components communicate through signaling pathways and physical contacts to regulate barrier properties, transport, and homeostasis.

In the neurovascular unit, endothelial cells form tight and adherens junctions that restrict paracellular diffusion, while astrocyte end-feet envelop the capillaries and release signaling molecules that influence barrier integrity and transporter expression. Glial cells, including microglia and oligodendrocyte lineage cells, participate in immune surveillance, ion buffering, and metabolic support. Key signaling pathways that mediate endothelialglial interactions include Wnt/beta-catenin, Sonic hedgehog, and transforming growth factor-beta, which help govern tight junction formation, transporter profiles (such as GLUT1 and efflux pumps), and endothelial permeability. Astrocytes also contribute to metabolic coupling and the regulation of the glymphatic system, a waste-clearance pathway linked to perivascular astrocytic processes.

Clinical relevance centers on BBB disruption and impaired endothelialglial signaling observed in stroke, multiple sclerosis, and neurodegenerative diseases. Research approaches combine in vitro co-culture systems, induced pluripotent stem cell–derived endothelial and glial cells, and organ-on-a-chip models to study communication pathways and test therapies aimed at restoring barrier function and CNS homeostasis.