UC San Diego

The blood-brain barrier (BBB) is a specialized set of features unique to the central nervous system vasculature that tightly regulates the movement of ions, molecules, and cells between the blood and the brain, maintaining neural homeostasis. BBB dysfunction is a hallmark of many neuroinflammatory conditions, including multiple sclerosis, traumatic brain injury, and stroke. One of the least understood components of the BBB is the glycocalyx, the dense layer of glycans and glycoconjugates that coats the luminal surface of the cerebral vasculature and serves as the first point of contact between the blood and brain. Though it may prove vital to our understanding of the BBB and offer new therapeutic targets to treat neuroinflammation, research into the BBB glycocalyx has been limited.This dissertation explores the BBB glycocalyx in health and neuroinflammation. By refining existing methods, we overcame key technical challenges, which enabled the first in-depth molecular analysis of the BBB glycocalyx. Our research revealed that the BBB glycocalyx has a highly unique glycan landscape with distinct structure, molecular composition, and function compared to glycocalyces in the peripheral vasculature. Notably, we found that the BBB glycocalyx is highly resilient, showing minimal structural and molecular changes across several models of neuroinflammation. Ultimately, this work advances our understanding of the BBB glycocalyx and offers new tools and targets for future research into its role in health and disease.