'Cell atlas' of brain vasculature!

The researchers have catalogued all the cells that form the blood vessels of the human brain, along with their locations and the genes transcribed in each. 

The atlas characterizes more than 40 previously unknown cell types, including a population of immune cells whose communication with the brain’s vascular cells contributes to the bleeding of a hemorrhagic stroke. This devastating form of stroke accounts for 10-15 percent of all strokes in the U.S., mostly among younger people. About half of hemorrhagic strokes are fatal.

The findings will serve as a foundation for new research on brain vasculature globally, the scientists said.

“This research gives us the map and the list of targets to start developing new therapies that could change the way we treat a lot of cerebrovascular diseases,” said one of the lead authors of the study, which appears in the journal Science.

The team analyzed cells in arteriovenous malformations, or AVMs, tangles of poorly formed arteries in the brain that are often the source of a hemorrhagic stroke. They compared the AVMs with samples of normal brain vasculature from five volunteers who were already undergoing brain surgery for epilepsy.

Some of the 44 samples of AVM tissue, acquired during delicate surgeries from the patient’s brain while still intact, and other samples were only removed after they had started to bleed. The three varieties of tissue—normal, intact AVMs, and AVMs that had bled—allowed the researchers to get a fuller picture of differences between how the cells function normally and in different states of disease. 

In collaboration with the Cerebrovascular Research Center, the team used single-cell mRNA sequencing on more than 180,000 cells to determine which genes were being expressed in the differing samples and matched gene expression with a cell’s location. The authors then developed computer analyses that compared gene expression in the normal and diseased cells. 

The results revealed not only a variety of new cell types, but a population of immune cells that appear to communicate with smooth muscle cells in the diseased arteries and weaken them, resulting in a stroke. Scientists have suspected that the immune system is activated by malformations like AVMs.

Identifying these specific immune cells completely changes how researchers can think about treating this sort of vascular disease, the author added. If the cells circulate in the blood, it may be possible to reduce stroke risk by modulating the immune system. 

“This opens up huge therapeutic potential,” said the author.

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

“Many forms of dementia, including Alzheimer’s, appear to have a vascular underpinning,” said the author. “We need an atlas like this to better understand how changes in the vasculature can contribute to the loss of cognition and memory.”

The authors believe that this information will allow researchers across the world to perform much less expensive analyses on large numbers of patients, which is the only way to get a fuller picture of how vascular diseases operate. 

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

While there is a lot of work taking place around the world to generate these atlases for different organs and tissues, many of them only map the geographic locations of cells. The comparison of normal and abnormal cells in this research takes it to a higher level, providing extremely refined guidance for drug development.