Proliferation of Distinct Hippocampal Progenitor Cells after Cortical Infarcts in the Adult Brain

Stimulation of cell proliferation and neurogenesis in the adult dentate gyrus has been observed following global and focal brain ischemia even when the hippocampal formation was not directly damaged. We here analyzed the effects of small cortical infarcts on proliferation of subpopulations of nestin-expressing progenitor cells during the first 3 days after ischemia using the photothrombosis model in adult transgenic pNestin-GFP-mice. Proliferating cells were labelled by a single i.p. injection of bromodeoxyuridine (BrdU, 50mg/kg) 2 hours after induction of the infarct and further characterized at 6, 24, and 72 hours after ischemia using immunocytochemistry and confocal laser scanning microscopy. Compared with sham-operated controls, animals with cortical infarcts showed the following alterations: (i) the number of BrdU-positive cells was significantly elevated after 6 hours; (ii) the slowly dividing nestin-positive cells with characteristic astrocytic features (type 1 cells) continuously increased their proliferative activity during the first postischemic days; (iii) the progenitor cells expressing the early neuronal marker doublecortin (type 2b and 3 cells) were only initially stimulated. Notably, the effects were observed in the ipsilateral as well as contralateral dentate gyrus. These findings indicate that focal ischemic infarcts differentially influence the proliferation of distinct subpopulations of progenitor cells during the first hours after the insult. In particular, type 1 cells with only minor proliferative activity under physiological conditions are stimulated by ischemic infarcts. Supported by DFG Re 1315/3–1.