Glial-endothelial crosstalk regulates blood–brain barrier function

• Radial glia provide the physical scaffolding and chemical signals to support BBB formation.
• Early astrocyte development relies on mechanical and chemical cues from ECs.
• Mature astrocytes nourish the BBB through physical contact and soluble factors.
• Reactive astrocytes release BBB-enhancing and BBB-disrupting soluble mediators.
• New therapies targeting astrocytes mitigate inflammation and promote BBB function.

The blood–brain barrier (BBB) is comprised of unique endothelial cells (ECs) that regulate the delicate central nervous system (CNS) microenvironment. During development, vasculature sprouts from the perivascular neural plexus and penetrates the CNS parenchyma. Recent studies indicate that these nascent vessels rely on radial glia (RG)-secreted factors for guidance and barrier induction. This early association also sustains astrocyte development, allowing for a tight interaction between these mature glia and ECs. The astrocyte–EC interface is crucial to BBB function and is substantially modified during pathology. Understanding the relationship between astrocytes and ECs lays the groundwork for advancing protective therapies that target neuroinflammatory disorders.