Effects of focal cerebral ischemia and neurotrophic factor on proliferation, migration and differentiation of ependymal neural stem cells in the lateral ventricle

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It has been proposed that ependymal cells (ECs) of the lateral ventricle (LV) are stem cells that undergo cell division to generate progenitor cells in the subventricular zone (SV) of LV that migrate and produce neuronal cells in the rostral migratory stream. The progenitor cells in SV have been reported to proliferate and differentiate after focal cerebral ischemia. The purpose of this study was to examine the response such as migration, proliferation and differentiation of EC to transient focal cerebral ischemia in the rat. To trace ECs 10 μl of 1, 1'-dioctadecyl-6, 6'-di(4-sulfophenyl)-3, 3, 3' ,3' -tetramethylindocarbocyanine (Dil), 0.2 %, was administered in the left LV, and 〜30 min later ischemia was induced by right middle cerebral artery occlusion (MCAO) for 90 min or sham operation was performed. Proliferating cells were labeled with bromodeoxyuridine (BrdU) over 2-day periods before sacrificing animals. In the separate experiment, basic fibroblast growth factor (bFGF) was con … More tinuously infused into the right LV at the rate of 1 μg / day for 3 days from the day of MCAO. Dil-labeled cells appeared in the striatum close to the ischemic lesion 7, 14, and 28 days after MCAO. The extent of migration of Dil-labeled cells was similar at 7, 14 and 28 days after MCAO. In contrast, only ECs of LV except for rostral migratory stream was labeled with Dil in sham-operated animals at any time point. Migrating Dil-labeled cells occasionally expressed immunoreactivity for Notch1, suggesting that these cells were originally derived from ECs. Immunohistochemistry for proliferating cell nuclear antigen and BrdU revealed that some Dil-labeled cells in the striatum were proliferating at 7 days after MCAO. However, these cells did not have immunoreactivity for βIII-tubulin, glial fibrillary acidic protein and O4 7, 14 and 28 days after MCAO. These findings suggest that ECs of LV wall generate immature cells such as precursor or progenitor cells, which migrate toward the lesion caused by transient focal ischemia. The protocol for bFGF administration used in this study did not show remarkable effects on the extent of migration of Dil-labeled cells and the infarct lesion. Less