Doublecortin-expressing cells in the ischemic penumbra of a small-vessel stroke.

A cortical lesion was induced by disrupting the medium-size pial vessels, which led to a cone-shaped cortical lesion and turned into a fluid-filled cavity surrounded by a glial acidic fibrillary protein-positive (GFAP(+)) glia limitans 21 days after injury. Therefore, it mimics conditions of lacunar infarctions, one of the most frequent human stroke pathologies. Doublecortin (DCX)-positive cells were present in the neocortex and corpus callosum at the base of the lesion. The number of DCX-positive cells in the corpus callosum was significantly increased from day 5 to day 14 compared with the control group. In contrast, there were no DCX-positive cells in neocortex of control animals; the DCX-positive cells appeared in the neocortex after lesioning and were maintained until 14 days postlesioning. Some of the DCX-positive cells were also immunoreactive for beta III-tubulin, another marker of immature neurons. They did not stain positively for markers of glia cells. The presence of these DCX-positive cells near the lesion might indicate a migratory pathway for developing neuroblasts from the subventricular zone (SVZ) through the corpus callosum to the lesion. SVZ cells were labeled with a lipophilic molecule, 5- (and 6-) carboxyfluorescein diacetate succinimidyl ester (CFSE) stereotaxical injections. Although rostral migratory stream and olfactory bulb were intensely labeled, no CFSE-containing cells were found in the cortex beneath the lesion. These results do not support the idea that the DCX-positive cells were originating from neural precursors of the SVZ, but they might be generated from local progenitor cells.