Early proliferative response of radial glia-like progenitor cells in the dentate gyrus following focal ischemia

Although brain insults such as stroke and epilepsy strongly increase proliferation of endogenous stem cells and neurogenesis in adult dentate gyrus, the underlying cellular mechanism are only poorly understood. Progenitor cells in the adult dentate gyrus do not constitute a homogenous population. Astrocytic cell types with radial glia-like morphology and low proliferative activity have been distinguished from highly dividing subtypes expressing early neuronal properties. Recent evidence indicates that physiological stimuli predominantly increase proliferation of non-astrocytic cell types whereas radial glia-like precursors remain quiescent. We here analyzed the proliferative response of these progenitor subtypes under pathophysiological conditions in a model of photochemical cortical infarcts. Using transgenic pNestin-GFP mice and single intraperitoneal injections of 5-bromo-2-deoxyuridine 4h after surgery, immunocytochemical analysis of the distinct cell types revealed a differential activation of all subpopulations within 72h after the infarct. The stimulation was most prominent in radial glia-like progenitor cells that are normally a slow dividing cell population and are considered as the putative stem cells in the hippocampus.

Supported by DFG Re1315/3–1, IZKF (TP1.7)