Microglia contact cerebral vasculature through gaps between astrocyte endfeet

• Published in: Journal of cerebral blood flow and metabolism p. 271678X241280775
• Main Authors: Morris, Gary P, Foster, Catherine G, Sutherland, Brad A, Grubb, Søren
• Format: Journal Article
• Language: English
• Published: 10.09.2024
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1177/0271678X241280775

The close spatial relationship between microglia and cerebral blood vessels implicates microglia in vascular development, homeostasis and disease. In this study we used the publicly available Cortical MM^3 electron microscopy dataset to systematically investigate microglial interactions with the vasculature. Our analysis revealed that approximately 20% of microglia formed direct contacts with blood vessels through gaps between adjacent astrocyte endfeet. We termed these contact points “plugs”. Plug-forming microglia exhibited closer proximity to blood vessels than non-plug forming microglia and formed multiple plugs, predominantly near the soma, ranging in surface area from ∼0.01 μm 2 to ∼15 μm 2 . Plugs were enriched at the venule end of the vascular tree and displayed a preference for contacting endothelial cells over pericytes at a ratio of 3:1. In summary, we provide novel insights into the ultrastructural relationship between microglia and the vasculature, laying a foundation for understanding how these contacts contribute to the functional cross-talk between microglia and cells of the vasculature in health and disease.