An international consortium of researchers, led by the University Health Network (UHN) in Toronto and the University of Zurich, has created the first molecular atlas of the human brain's vasculature with unprecedented resolution.
This advanced atlas reflects several stages, from early development to adulthood as well as disease stages, such as brain tumors and cerebrovascular malformations.
In the study, the researchers isolated blood vessels from early developing human brains, adult brains, brain tumors, and brain vascular malformations.
They found that endothelial cells, which line blood vessels and regulate interactions between the bloodstream and surrounding tissues, vary in their effectiveness across different stages of brain development, and may have an important, "undiscovered" role within the brain's neurovascular signaling networks.
“Brain blood vessels, genes and pathways are important for proper brain function in early development and adulthood, as well as for a variety of brain diseases, such as tumors, stroke and brain vascular malformations,” said study author Dr. Thomas Walshley, a scientific fellow at the UHN Krempel Brain Institute.
“By understanding how these pathways develop and behave during early brain development, how they are silenced in the healthy adult brain, and how they are reactivated in disease states, researchers can gain insight into the normal functioning of blood vessels in the human brain, opening doors to future therapeutic options,” he added.
“We were able to sequence the RNA at the single-cell level of more than 600,000 isolated endothelial and perivascular cells from 117 samples, with unprecedented resolution, giving us an amazing look at the inner workings of the brain’s blood vessels,” explained Dr. Ivan Radovanovic, a neurosurgeon and co-author of the study.
Radovanovic noted that revealing the key differences between “healthy” and diseased brain blood vessels could help identify vulnerabilities in abnormal brain vessels that could be used to treat both brain tumors and blood vessel malformations.
The researchers found that blood vessels in the healthy adult brain stop growing almost completely over time, but a brain tumor or vascular malformation can reactivate blood vessel growth in brain tissue, similar to blood vessel growth in the early developing brain.
For the first time, the research team has shown how blood vessels in the human brain differ from those in organs outside the brain, both during early brain development and in adulthood. When disease develops, blood vessels in the brain become more like those in a peripheral organ.
“Our work will benefit researchers across disciplines, from developmental, vascular and oncology biologists to neuroscientists, immunologists and single-cell geneticists,” adds Al-Washli.
The study was published in the journal Nature.
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