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.
Original language | English |
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Pages (from-to) | 826-842 |
Number of pages | 17 |
Journal | Journal of Neuroscience Research |
Volume | 98 |
Issue number | 5 |
Early online date | 2019 Nov 22 |
DOIs | |
Publication status | Published - 2020 May |
Subject classification (UKÄ)
- Neurosciences
Free 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