Activation and proliferation of oligodendrocyte progenitor cells after brain ischemia in the rat

Abstract

The present study examined the alteration of oligodendrocyte progenitor cells (OPCs), which were identified with the expression of membrane neuron glial antigen 2 (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. Stellate-shaped OPCs with multiple branched processes were abundantly detected in both the gray and white matter of normal brain. After 2 weeks of recirculation, OPCs in peri-infarct area clearly showed enlarged cell bodies with hypertrophied processes, which were accompanied by reappearance of mature oligodendrocytes and restoration of myelination in this area. These OPCs stained strongly for NG2, but not for the specific markers of neurons, astrocytes, microglia and mature oligodendrocytes. The number of OPCs was significantly increased in the peri-infarct area, whereas neither any sign of activation nor proliferation of OPCs was detected in the subventricular zone and the granular layer of the dentate gyrus, suggesting that the activation of OPCs occurred locally in the peri-infarct area. Phosphorylation of cyclic AMP response element binding protein (CREB) was clearly enhanced in these activated OPCs. Since OPCs are known to revert to neural stem cells, the upregulation of OPCs may be an adaptive mechanism attempting to remyelinate or reorganize brain tissue after ischemic insult.