Activation of NG2-Positive Oligodendrocyte Progenitor Cells after Focal Ischemia in Rat Brain

Abstract

The present study examines the alteration of oligodendrocyte progenitor cells which express membrane NG2 chondroitin sulfate proteoglycan after focal ischemia in the rat brain. Adult male Sprague-Dawley rats were subjected to 90-min occlusion of the middle cerebral artery, followed by recirculation time of up to 2 weeks. The distribution and morphological changes in NG2-positive oligodendrocyte progenitor cells were immunohistochemically examined. Stellate-shaped NG2-positive cells with multiple branched processes were abundantly detected in both the gray and white matter of normal brain. After two weeks of recirculation, NG2-positive cells in the area surrounding the infarction site (peri-infarct area) clearly showed enlarged cell bodies with hypertrophied processes. These stained strongly for NG2. Although the number of NG2-positive cells was significantly increased in the peri-infarct area, it was markedly decreased in the infarct core compared to controls. Double immunostaining revealed that these NG2-positive cells were not astrocytes, microglia or mature oligodendrocytes, but NG2-positive oligodendrocyte progenitor cells. Phosphorylation of CREB (cyclic AMP response element-binding protein) was clearly enhanced in these activated NG2-positive cells. These progenitor cells are known to revert to neural stem cells, which can give rise to neurons and astrocytes, as well as to oligodendrocytes. As such, this upregulation of NG2-positive progenitor cells may be an adaptive mechanism attempting to remyelinate or reorganize rat brain tissue after ischemic insult.