Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice

• Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet-derived growth factor receptor ß-expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß+ cells due to the loss of regulator of G-protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß+ cells co-label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß+ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß+ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß+ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

collagen

extracellular matrix

fibronectin

fibrotic scar

glial scar

pericytes

RRID:AB_2082660

RRID:AB_2105706

RRID:AB_2162497

RRID:AB_217595

RRID:AB_2298772

RRID:AB_298179

RRID:AB_305808

RRID:AB_354858

RRID:AB_393571

RRID:AB_467492

RRID:SCR_002798

RRID:SCR_003070

RRID:SCR_010279

stroke

Publication and Content Type

art (subject category)

ref (subject category)