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Ischemic stroke induces neurogenesis in the subventricular zone (SVZ), and newly generated neurons in the SVZ migrate toward the ischemic boundary. However, the characteristics of migrating SVZ cells have not been investigated after stroke. Using time-lapse imaging in both SVZ cells and organotypic brain slice cultures, we measured the dynamics of SVZ cell division and migration of adult rats subjected to stroke. In normal brain slices, SVZ cells primarily migrated dorsally and ventrally along the lateral ventricular surface. However, in stroke brain slices, SVZ cells migrated laterally toward the striatal ischemic boundary. Cultured stroke-derived SVZ cells exhibited a significant (p<0.01) increase in the migration distance (212 ± 21 µm)compared with the nonstroke-derived SVZ cells (97 ± 12 µm). Migrating stroke-derived SVZ cells spent significantly (p = 0.01) less time in cytokinesis (0.63 ± 0.04 h) compared with the time (1.09 ± 0.09 h) for nonstroke-derived SVZ cells. Newborn cells with a single leading process exhibited fast migration (7.2 ± 0.8 µm/h), and cells with multiple processes showed stationary migration (3.6 ± 0.8 µm/h). Stroke SVZ daughter cells further divided during their migration. The morphology of doublecortin (DCX)-positive cells in fixed brain sections resembled those observed in cultured newborn cells, and the DCX-positive cells proliferated in the ischemic striatum. Collectively, the present study suggests that stroke promotes cytokinesis of migrating neuroblasts, and these cells migrate toward the ischemic striatum with distinct migratory behaviors and retain the capacity for cell division during migration. [ABSTRACT FROM AUTHOR]

The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55% of dividing cells were oriented horizontally, whereas 40% were oriented vertically. Horizontal and vertical cleavage orientations produce asymmetric and symmetric divisions, respectively. Four days after stroke, the number of dividing cells increased twofold, whereas the proportion of symmetric dividing cells significantly (p < 0.01) increased from 40% before stroke to 60%. Fourteen days after stroke, the percentage of symmetric dividing cells was 47%. Stroke-increased numbers of dividing cells in M-phase were confirmed by immuostaining. In nonstroke rats, 37 and 33% of symmetric and asymmetric dividing cells, respectively, exhibited a neuronal marker (TuJ1). Four days after stroke, rats exhibited a significant (p < 0.05) augmentation of the frequency (47%) of neuronal distribution showing TuJ1 immunoreactivity in ceils with symmetric division but not ceils with asymmetric division (33%). Numb immunoreactivity was detected in SVZ cells of nonstroke rats. Stroke did not change Numb distribution. Our data suggest that neurons are produced by both asymmetric and symmetric cell divisions in the adult SVZ, and the transient increases in symmetric division and neuronal differentiation may result in stroke-induced neurogenesis. [ABSTRACT FROM AUTHOR]

Using magnetic resonance imaging (MRI), we described a method for noninvasively tracking grafted neural progenitor cells and bone marrow stromal cells (MSCs) in brain tumor of the rat. Neural progenitor cells and MSCs were labeled with lipophilic dye-coated superparamagnetic particles. The labeled neural progenitor cells and MSCs were transplanted to rats via the cisterna magna and a tail vein, respectively, 1 week after 9L-gliosarcoma cell implantation. Three-dimensional (3D) gradient echo and contrast agent images revealed dynamic migration of adult neural progenitor cells and MSCs detected by loss of MRI signals towards tumor mass and infiltrated tumor cells. Prussian blue staining and fluorescent microscope analysis showed that grafted cells targeted tumor cells and areas with grafted cells corresponded to areas with loss of MRI signals. These results demonstrate that the MRI technique provides a sensitive method for in vivo assessment of grafted cells targeting tumor mass and infiltrated tumor cells and that adult neural progenitor cells and MSCs can target tumor aggregates in the brain. [Copyright &y& Elsevier]