Abstract
BackgroundPerivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the CNS perivascular space. PSCs are activated following injury to the brain or spinal cord, expand in number and contribute to fibrotic scar formation within the injury site. Beyond fibrosis, their high density in the lesion core makes them a potential significant source of signals that act on neural cells adjacent to the lesion site.ResultsOur developmental analysis of PSCs, defined by expression of Collagen1a1 in the maturing brain, revealed that PSCs first appear postnatally and may originate from the meninges. PSCs express many of the same markers as meningeal fibroblasts, including expression of the retinoic acid (RA) synthesis proteins Raldh1 and Raldh2. Using a focal brain ischemia injury model to induce PSC activation and expansion, we show a substantial increase in Raldh1+/Raldh2+ PSCs and Raldh1+ activated macrophages in the lesion core. We find that RA levels are significantly elevated in the ischemic hemisphere and induce signaling in astrocytes and neurons in the peri-infarct region.ConclusionsThis study highlights a dual role for activated, non-neural cells where PSCs deposit fibrotic ECM proteins and, along with macrophages, act as a potentially important source of RA, a potent signaling molecule that could influence recovery events in a neuroprotective fashion following brain injury.
Highlights
Perivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the central nervous system (CNS) perivascular space
Temporal and spatial distribution of Col1a1+ PSCs in the early postnatal mouse brain The Col1a1-green fluorescent protein (GFP) transgenic line has been used to identify a subset of perivascular cells that dramatically expand in number in response to a spinal cord injury [48] that have the same characteristics of PSCs described in stroke injury [9]
PSCs dynamically express both pericyte and meningeal cell markers The positional analysis of Col1a1+ cell distribution suggested that PSCs may originate from the meninges, we examined expression of meningeal cell markers within this population at postnatal day 0 (P0) when PSCs are first observed in the mouse brain and in PSCs in the more mature brain at postnatal day 21 (P21)
Summary
Perivascular stromal cells (PSCs) are a recently identified cell type that comprises a small percentage of the platelet derived growth factor receptor-β+ cells within the CNS perivascular space. Pericyte-like cells termed perivascular stromal cells (PSCs) or type “A” pericytes have been identified as a major source of ECM proteins that generate the fibrotic scar, separate from the well-characterized astroglial scar, within the injured CNS tissue following both spinal cord and stroke injury [9, 11, 31, 48] Beyond their role in fibrotic scar formation, PSCs in the lesion core are uniquely. A few unique and defining characteristics of PSCs have been reported These include (1) expression of platelet derived growth factor receptor-β (PDGFrβ), but not the pericyte marker desmin and (2) they are labeled in GLAST-CreErt [11] and Collagen1a1-GFP (Col1a1-GFP) [48] transgenic mouse lines. In addition to lineage ambiguity, developmental characterization of PSCs is
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