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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Karolinska Institutet
  • Skåne University Hospital
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • 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
Original languageEnglish
JournalJournal of Neuroscience Research
Publication statusE-pub ahead of print - 2019 Nov 22
Publication categoryResearch
Peer-reviewedYes