Temporal dynamics of cells expressing NG2 and platelet-derived growth factor receptor-β in the fibrotic scar formation after 3-nitropropionic acid-induced acute brain injury

Neuron-glia antigen 2 (NG2) proteoglycan and platelet-derived growth factor receptor beta (PDGFR-β) are widely used markers of pericytes, which are considered cells that form fibrotic scars in response to central nervous system insults. However, the exact phenotypes of NG2- and PDGFR-β-expressing cells, as well as the origin of the fibrotic scar after central nervous system insults, are still elusive. In the present study, we directly examined the identities and distributions of NG2- and PDGFR-β-positive cells in the control and lesioned striatum injured by the mitochondrial toxin 3-nitropropionic acid. Immunoelectron microscopy and correlative light and electron microscopy clearly distinguished NG2 and PDGFR-β expression in the vasculature during the post-injury period. Vascular smooth muscle cells and pericytes expressed NG2, which was prominently increased after the injury. NG2 expression was restricted to these vascular mural cells until 14 days post-lesion. By contrast, PDGFR-β-positive cells were perivascular fibroblasts located abluminal to smooth muscle cells or pericytes. These PDGFR-β-expressing cells formed extravascular networks associated with collagen fibrils at 14 days post-lesion. We also found that in the injured striatal parenchyma, PDGFR-β could be used as a complementary marker of resting and reactive NG2 glia because activated microglia/macrophages shared only the NG2 expression with NG2 glia in the lesioned striatum. These data indicate that NG2 and PDGFR-β label different vascular mural and parenchymal cells in the healthy and injured brain, suggesting that fibrotic scar-forming cells most likely originate in PDGFR-β-positive perivascular fibroblasts rather than in NG2-positive pericytes.