Fig. 4.

Migration in vitro of NSCs from subventricular zone toward explants from ischemic brain is mediated by SDF-1α–CXCR4 interaction. (a) Mouse NSCs (nestin+) that migrate chain-like toward ischemic brain explants express CXCR4. The phase image is shown under fluorescence microscopy below it, dual immunostained for nestin (green) and CXCR4 (red). (b) The area demarcated by the box in a, near the ischemic explant (asterisk), the border of which is indicated by the dotted line, is magnified where the nestin+ NSCs (green) are noted to coexpress CXCR4 (red); dual-immunoreactive cells seen as yellow in merged image. (c Left) Minimal chain migration of nestin+ cells to the contralateral noninjured explant correlating with an absence of SDF-1α in the explant, preserved only in meninges (arrow). (c Right) Robust migration of nestin+ NSCs toward injured explant with an increase in polarization and number of chains (see Figs. 6 and 7). (d) Neurospheres confronted with explants (asterisk) from normal control hemispheres show no migration (Left), neurospheres confronted at the same distance with explants from an ischemic hemisphere (asterisk) elaborate processes containing chains of migrating NSCs directed toward the explants (arrows) (Center); these behaviors are abrogated in neurospheres confronted with an ischemic explant (asterisk) but treated with a purified blocking antibody to CXCR4 (10 μg per explant) (Right). (e) Quantification of the percent of neurospheres with directed migration toward the explants. (f) Quantification of the formation of migratory chains toward the following explants: control, ischemic, or ischemic treated with anti-CXCR4 antibody. The latter condition reduces the number of migratory chains (P < 0.001).