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Cell-level atlas maps out brain's blood vessels

By Nicholas Gerbis
Published: Friday, January 28, 2022 - 1:21pm
Updated: Friday, January 28, 2022 - 1:35pm
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Barrow Neurological Institute
Ethan Winkler, an endovascular fellow at Barrow Neurological Institute

Scientists and physicians around the world are working to produce cell-level atlases of bodily organs.

A new study in the journal Science extends that effort to a largely overlooked aspect of the brain: the blood vessels that move oxygen and nutrients and remove toxins and waste products.

Studying organs often entails focusing on one cell type while ignoring others. In the brain, many of those castoff cells belong to the branching, specialized vasculature network, despite its key role in illnesses like stroke and Alzheimer's disease.

"A lot of these isolation procedures that have been used in previous works have just simply not collected vascular cells, and they've been slanted more to studying the neurons and the glia," said lead author Ethan Winkler, an endovascular fellow at Barrow Neurological Institute.

Dissecting and sequencing more than 180,000 cells from the cerebral cortexes of patients undergoing tailored lobectomies for epilepsy, the team cataloged an array of vascular cells, networks and gene activity that could help guide treatments.

"There had been some studies done in mice that had shown unexpectedly that there was an expanded cell variation or diversity in the mouse cerebral vasculature. However, the real cell composition of the human cerebral vasculature was largely unexplored," said Winkler.

The team found a similar variety in the cell structures that make up the arteries, capillaries, veins and other vessels in human brains, each suited to that vessel's purpose. Such information could help researchers understand why neurologic diseases like stroke, Alzheimer's disease or brain aging seem to prefer particular segments of blood vessels.

"There's actually an expanded variety of different cell types within the vasculature. And we actually now have molecular coordinates or specific genes that are expressed in each one of these cell types that may pave the way for future therapeutic targeting," said Winkler.

The team also used its findings to study brain arteriovenous malformations, abnormal tangles of blood vessels that can cause hemorrhagic stroke in young people.

"We have now cataloged all of those abnormalities, as well as some predicted interactions between the cells, and uncovered a immune cell population that we think is very important to actually causing these things to bleed," said Winkler.

Winkler added that this was just the first step. Building the atlas out further will require investigators across the globe delving into related questions, such as how cell composition varies from one vascular region to another, and studying blood vessels at various phases of life, not just middle aged adults.

"This was one effort, and it's really going to take an effort by many to hopefully change the way that we end up approaching cerebrovascular diseases and neurologic diseases in general," he said.

Science