4.6 Article

Distinct features of brain perivascular fibroblasts and mural cells revealed by in vivo two-photon imaging

Journal

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 42, Issue 6, Pages 966-978

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X211068528

Keywords

Perivascular fibroblasts; collagen-1; pericytes; smooth muscle cells; brain vasculature

Funding

  1. NIH NRSA fellowship [F32 NS117649, NS119615, NS106138, AG063031, NS097775]

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The study identified the distribution and characteristics of perivascular fibroblasts (PVFs) in the cerebral cortex, providing clarity on their differences with mural cells and addressing the challenge of distinguishing between the two cell types.
Perivascular fibroblasts (PVFs) are recognized for their pro-fibrotic role in many central nervous system disorders. Like mural cells, PVFs surround blood vessels and express Pdgfr beta. However, these shared attributes hinder the ability to distinguish PVFs from mural cells. We used in vivo two-photon imaging and transgenic mice with PVF-targeting promoters (Col1a1 or Col1a2) to compare the structure and distribution of PVFs and mural cells in cerebral cortex of healthy, adult mice. We show that PVFs localize to all cortical penetrating arterioles and their offshoots (arteriole-capillary transition zone), as well as the main trunk of only larger ascending venules. However, the capillary zone is devoid of PVF coverage. PVFs display short-range mobility along the vessel wall and exhibit distinct structural features (flattened somata and thin ruffled processes) not seen with smooth muscle cells or pericytes. These findings clarify that PVFs and mural cells are distinct cell types coexisting in a similar perivascular niche.

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