Nestin-expressing cells divide and adopt a complex electrophysiologic phenotype after transient brain ischemia.

The intermediate filament nestin is upregulated in response to cerebral ischemia; the significance of this, however, is incompletely understood. Here, we used transgenic mice that express green fluorescent protein (GFP) under control of the nestin promotor to characterize the fate of nestin-expressing cells up to 8 weeks after 30 mins occlusion of the middle cerebral artery (MCAo) and reperfusion. The population of nestin-GFP+ cells increased in the ischemic lesion rim and core within 4 days, did not become TUNEL-positive, and was detectable up to 8 weeks in the lesion scar. Nestin-GFP+ cells proliferated in situ and underwent approximately one round of cell division. They were not recruited in large numbers from the subventricular zone (SVZ) as indicated by absence of colabeling with intracerebroventricularly injected dye DiI in the majority of nestin-GFP+ cells. Nestin-GFP+ cells expressed the chondroitin sulfate proteoglycan NG2 and nestin protein, but typically lacked mature astrocytic markers, that is, glial fibrillary acid protein (GFAP) or S100beta. Vice versa, the majority of GFAP+ cells lacked nestin-expression and surrounded the ischemic lesion by 4 days. Whole-cell patch-clamp recordings in acute brain slices from controls showed that only about half of nestin-GFP+ cells displayed complex membrane properties. In contrast, 4 days after the insult all nestin-GFP+ cells expressed these properties. We hypothesize that the change in physiologic properties induced by the ischemic insult is directed toward a specific function of nestin-expressing cells.