Accumulating evidence has shown that endogenous neurogenesis is developing even in adult central nervous system (CNS). We also have isolated neural stem/progenitor cells induced by cerebral ischemia (iNSPC) (Eur J Neurosci, 2009), suggesting the neurogenesis at post-stroke brain. However, identification of their origin is not clarified, although a part of iNSPC comes from the brain pericytes (Stem Cell Dev, 2011). In addition their capability to differentiate into other lineages is not examined. NG2 is known as a marker of pericytes as well as oligodendrocyte precurcer cells (OPC) and microglia. In this study we examined whether iNSPC consisting of NG2-expressing cells could differentiate into microglia as well as neural cells using NG2-red fluorescent protein (RFP) transgenic rats.

Focal cerebral ischemia was produced by occluding the middle cerebral artery of adult NG2-RFP transgenic rats. Animals were fixed 3 days after stroke and brain sections were subjected to immunohistochemistry for RFP, nestin, CD31, PDGFRα, PDGFRβ, or Iba1. Double immunofluorescence showed that NG2/RFP cells expressed PDGFRβ, but not nestin in non-ischemic cortex. In the ischemic region, however, some of them expressed nestin, PDGFRα, Iba1 as well as PDGFRβ.These cells were in close association to the CD31-positive endothelial cells. The iNSPC/neurosphere produced from the ischemic region of rats were consisted of RFP-positive cells, and differentiated into MAP2-positive neurons, MAG-positive oligodendrocytes and Iba1-positive microglia.

These results suggest that some NG2-expressing cells are pericytes, and they differentiate into all components of CNS after stroke. Although the precise characteristics of NG2 cells are still unknown, the present study suggests the new mechanism for repairing CNS by NG2-expressing cells in post-stroke brain.