Although the brain is crisscrossed with blood vessels bringing a constant supply of oxygen and nutrients, it’s also a fortress. Each capillary is lined with a barrier that only select molecules can cross, which protects the brain but poses a formidable hurdle for neuroscience drug development.
To better understand the composition of the blood-brain barrier, researchers led by Jiefu Li at the Howard Hughes Medical Institute developed a technique to label the inside surface of blood vessels and track how the blood-brain barrier of mice changes over time (Science 2026, DOI: 10.1126/science.aea2100).
The team used a glycan-binding lectin to anchor a proximity labeling system to the vascular surface. The labeling system tags nearby proteins with biotin for multiplexed proteomics analysis. This allowed the researchers to clock a reduction in vessel growth proteins during the transition to adulthood and an increase in inflammation-related adhesion molecules later in life.
Researchers used microscopy to confirm that their approach only labeled blood vessels and to quantify leaks Credit:
Science
One seemingly paradoxical finding was that hyaluronidase, the enzyme that breaks down the extracellular matrix polysaccharide hyaluronan, is required for barrier integrity. The researchers confirmed that the enzyme’s activity is required and that hyaluronan builds up when hyaluronidase is missing.
Just how accumulation of a viscous glycan better known for blocking diffusion can lead to a leakier membrane is yet to be determined. But the study adds to a growing literature on the glycans of the blood-brain barrier and how they shift with age.
Laurel Oldach is a senior editor and life sciences reporter at C&EN.
2026 American Chemical Society
