A new study led by UBC faculty of medicine researchers is shedding light on how the brain begins to heal itself after a stroke, identifying the specific brain cells that help to rebuild blood vessels and repair damaged tissue.
The study, recently published in Nature Neuroscience, investigated the role of stromal progenitor cells (SPCs), a group of brain cells that includes pericytes and perivascular fibroblasts. By tracking these cells in the brains of mice, the researchers reveal how they act as ‘repair specialists’ with pericytes promoting the formation of new blood vessels and perivascular fibroblasts creating protective scar tissue.
The discovery of these cells’ functions could pave the way for therapies that enhance natural healing processes and improve outcomes for stroke patients.
“Stroke recovery is a race against time. Understanding how the brain orchestrates its natural repair mechanisms gives us an opportunity to intervene and improve outcomes,” said senior author Dr. Brian MacVicar, a professor of psychiatry at UBC’s faculty of medicine and member of the Djavad Mowafaghian Centre for Brain Health.
Building blocks of brain repair
A stroke occurs when blood flow to part of the brain is interrupted, causing widespread cell death. Recovery depends on repairing the affected tissue and re-establishing blood flow to provide nutrients and oxygen
Using advanced genetic tools, the UBC researchers tracked the activity of SPCs in mice before and after a stroke. Their findings revealed that these cells transform their roles to meet the demands of a brain injury. Within days of a stroke, pericytes migrated to the damaged area, adopting a temporary role in creating new blood vessels, similar to their role in brain development during infancy.
“We were amazed to see pericytes essentially return to their developmental state, working alongside endothelial cells to rebuild the brain’s vascular network,” said lead author Dr. Louis-Philippe Bernier, a research associate in the MacVicar lab.
Meanwhile, perivascular fibroblasts focused on forming scar tissue. This scarring acts as a barrier, preventing further damage, but can also potentially inhibit neuronal regrowth.
A key finding was the importance of balancing the response of these two cell types. Too much scarring could block functional recovery, while insufficient scarring might leave the brain vulnerable to further damage.
“Revascularization is essential for recovery because restored blood flow brings the nutrients and oxygen needed to regenerate neural tissue,” Dr. MacVicar explained. “On the other hand, scar formation, while often seen as a barrier to recovery, plays a vital structural role in stabilizing the injury site.”
Translating findings into therapies
Through a detailed genetic analysis, the research team identified several key genes and pathways that drive the SPCs’ healing activities. By modulating these pathways, it might be possible to amplify the brain’s natural repair processes, making them promising therapeutic targets.
The findings could help to develop treatments that enhance the beneficial roles of SPCs while minimizing their drawbacks. For example, therapies might be designed to boost pericyte-driven blood vessel formation, while controlling excessive fibroblast-driven scarring.
While the research was conducted in mice, the findings mark a significant advancement in understanding how the brain heals after injury and could have profound implications for human stroke recovery.
“By uncovering how these cells work together to repair the brain, we’ve opened the door to new therapeutic possibilities,” Dr. Bernier notes. “With further research, we hope to translate these findings into treatments that will ultimately help improve recovery for stroke patients.”
The team has made their data publicly available through an online database, allowing other researchers to explore the genetic and molecular mechanisms of brain repair.
A version of this story was originally published on the Djavad Mowafaghian Centre for Brain Health website.