How the brain heals itself: UBC researchers identify key cells that help with stroke recovery

Dr. Brian MacVicar

A groundbreaking study led by UBC researchers sheds light on how the brain begins to heal itself after a stroke, offering new hope for improving recovery. In a new paper published in Nature Neuroscience, Dr. Brian MacVicar and his team have identified specific brain cells that play critical roles in rebuilding blood vessels and repairing tissue. This discovery could pave the way for therapies that enhance natural healing processes and improve outcomes for stroke patients.

The study, led by Dr. Louis-Philippe Bernier, a research associate in the MacVicar lab, focused on investigating the role of stromal progenitor cells (SPCs), a group of brain cells that include pericytes and perivascular fibroblasts. These cells act as repair specialists, taking on different tasks following a stroke. Pericytes promote the formation of new blood vessels (in a process called angiogenesis), while perivascular fibroblasts create protective scar tissue to stabilize damaged areas (in a process called fibrogenesis). Striking the right balance between these two processes is crucial for recovery.

“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 Dr. MacVicar, a Professor in the Department of Psychiatry and member of the Djavad Mowafaghian Centre for Brain Health.

Building blocks of brain repair

Dr. Louis-Philippe Bernier

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. Until now, the mechanisms underlying this repair have been poorly understood.

Using advanced genetic tools, Drs. Bernier and MacVicar, along with researchers in UBC’s Biomedical Research Centre, 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 angiogenic profile and helping to create 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 Dr. Bernier.

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 delicate balance

A key finding of the study was the importance of balancing the two key roles played by SPCs: promoting blood vessel growth while managing scar formation. 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.”

Stromal progenitor cells (SPCs) called pericytes (shown in red), gather at the edge of the injured area to aid in the formation of new blood vessels.

Translating findings into therapies

The research team’s detailed genetic analysis identified potential therapeutic targets, with several key genes and pathways found to drive the healing activities of SPCs. By modulating these pathways, it might be possible to amplify the brain’s natural repair processes. 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.

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 angiogenesis while controlling excessive fibroblast-driven scarring.

A step forward in stroke recovery

This study marks a significant advancement in understanding how the brain heals after injury. While the research was conducted in mice, the findings 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.”