Researchers have created the first molecular atlas of the human brain’s vasculature at the single-cell level, covering early development, adulthood, and disease stages like brain tumors and vascular malformations.
An international team of researchers, led by University Health Network (UHN) in Toronto and University of Zurich, has developed the initial molecular atlas of the human brain’s vasculature at single-cell resolution. The study spans from early brain development to adulthood and various disease stages such as brain tumors and vascular malformations.
The consortium includes researchers from UHN’s Krembil Brain Institute, Donald K. Johnson Eye Institute, Toronto General Hospital Research Institute, Princess Margaret Cancer Centre, University of Toronto’s Donnelly Centre, Mount Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute, University of Zurich, University Hospital Zurich, ETH Zurich, University of Geneva, University Hospital Geneva, as well as collaborators at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center in New York.
The research involved isolating blood vessels from developing brains, adult brains, brain tumors, and vascular malformations. It revealed that endothelial cells, which line blood vessels and control interactions between the blood and surrounding tissues, exhibit different behaviors during brain development stages, suggesting a more crucial role in the brain’s neurovascular signaling networks than previously thought.
This groundbreaking study has been published in Nature.
Dr. Thomas Wälchli, the study’s corresponding author, from UHN’s Krembil Brain Institute and University College London, stated, “Understanding the growth and behavior of these pathways during brain development and disease progression offers insights into the normal function of the brain’s vasculature and potential future therapeutic approaches.”
Dr. Ivan Radovanovic, a senior scientist at UHN’s Krembil Brain Institute and co-author of the study, mentioned the significance of the study’s large dataset in aiding researchers globally to identify distinctions between healthy and diseased brain vasculature for potential treatment strategies against brain tumors and vascular malformations.
The team’s key findings include:
- Brain tumors and vascular malformations can reactivate blood vessel growth within brain tissues similarly to early developing brains, a previously unreported phenomenon.
- The brain’s vasculature differs from that of peripheral organs, especially during disease states, making it more similar to peripheral organ vasculature.
- In disease conditions, the characteristics of brain vasculature, such as endothelial cells at the blood-brain barrier, can change, triggering immune responses and altering interactions with the body’s immune system.
The research may pave the way for potential therapeutic interventions by targeting vascular growth and enhancing the immune response to inhibit disease progression and improve patient outcomes.
Dr. Wälchli highlighted the possibility of combining vascular-targeting therapies with immunotherapies in the future to halt vascular growth and enhance patient survival rates.
The researchers aim to continue advancing the field of brain vascular biology and hope that their work will benefit a wide range of scientists in various disciplines.
“Our study has the potential to impact researchers from different backgrounds, including vascular and tumor biologists, neuroscientists, immunologists, and geneticists,” Dr. Wälchli concluded. “The opportunities for further exploration are vast.”
