Brain atlas reveals immune cells responsible for most strokes

An atlas that has cataloged all the cells that make up the blood vessels of the human brain has identified a hitherto unknown group of cells that are involved in lhemorrhagic strokes or stroke.

The work, which is published in «
», not only characterizes more than 40 previously unknown cell types, including this population of immune cells whose communication with vascular cells in the brain contributes to stroke, but it completely changes the way researchers can think about treating this type of vascular disease, opening a therapeutic window for these illnesses.

Hemorrhagic stroke is a disease that primarily affects people

younger. About half of hemorrhagic strokes are fatal.

That is why the relevance of these results, since they will also serve as a basis for new research on the cerebral vasculature, point out the scientists from the
University of California-San Francisco

«Research gives us the map and the checklist to start developing new therapies that could change the way we treat many cerebrovascular diseases», says Ethan Winkler, neurosurgeon and one of the main authors of the study.

Hemorrhagic stroke is a disease that mainly affects younger people

The researchers looked at cells present in arteriovenous malformations, tangles of misshapen arteries in the brain that are often the cause of hemorrhagic stroke.

They then compared these venous malformations with samples of normal brain vasculature from five volunteers who were undergoing brain surgery to treat epilepsy.

Some of the 44 tissue samples from these malformations were removed from the patient’s brain while they were still intact, while other samples were only obtained after they started bleeding.

venous malformations

The three varieties of tissue obtained – normal and intact and hemorrhagic – allowed the researchers to obtain a more complete picture of the differences between cells in normal function and in different disease states.

In collaboration with the Center for Cerebrovascular Research at UCF, the team used single-cell mRNA sequencing in more than 180,000 cells to determine which genes were expressed in the different samples and match gene expression with the location of a cell.

Using computer analysis, they then compared gene expression in normal and diseased cells.

The results revealed not only this new variety of new cell types, but also a population of immune cells that appear to communicate with smooth muscle cells in diseased arteries and weaken them, causing a stroke.

Scientists have long suspected that the immune system is activated by malformations, such as arteriovenous malformations.

But as Tomasz Nowakowski, one of the researchers in the article, explains, without this study, “we would not be able to identify this very specific population of cells in the blood that seem to be the key drivers of disease progression.”

If the cells circulate in the blood, then it is possible to reduce the risk of stroke by modulating the immune system. This opens up enormous therapeutic potential.

Now, the identification of these specific immune cells completely changes the way researchers can think about treating this type of vascular disease. “If the cells circulate in the blood, then it is possible to reduce the risk of stroke by modulating the immune system. This opens up enormous therapeutic potential,” says Nowakowski.

Furthermore, that potential extends beyond stroke. The atlas can help investigate any neurovascular disease, including one of the most common: dementia.

“Many forms of dementia, including Alzheimer’s disease, appear to have a vascular basis,” says Chang Kim, co-senior author of the study. «We need an atlas like this to better understand how changes in the vasculature may contribute to cognition and memory loss.».

Nowakowski believes this information will allow researchers around the world to perform much less expensive tests on large numbers of patients, which is the only way to get a more complete picture of how vascular disease works.

Cell Periodic Table

Finally, this team study contributes to the
Human Cell Atlas
, an international effort to create cell reference maps for the entire body.

The researchers have named their atlas ‘periodic table of cell typesThus, in the same way that the chemical periodic table organizes elements into a structure that allows chemists to establish relationships between them based on where they appear in the table, human cell atlases reveal the location of cells in the body and the resulting interactions between them.

‘Our study demonstrates how a cell atlas can be used. With our ‘periodic table’ as a reference, we can start to ask which cells might be failing in disease and target those cells very precisely.”

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