title: Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after focal cerebral ischemia.
abstract: In the adult rodent, stroke induces an increase in endogenous neural progenitor cell (NPC) proliferation in the subventricular zone (SVZ) and neuroblasts migrate towards the ischemic boundary. We investigated the role of stromal cell-derived factor 1alpha (SDF-1alpha) in mediating NPC migration after stroke. We found that cultured NPCs harvested from the normal adult SVZ, when they were overlaid onto stroke brain slices, exhibited significantly (P<0.01) increased migration (67.2+/-25.2 microm) compared with the migration on normal brain slices (29.5+/-29.5 microm). Immunohistochemistry showed that CXCR 4, a receptor of SDF-1alpha, is expressed in the NPCs and migrating neuroblasts in stroke brain. Blocking SDF-1alpha by a neutralizing antibody against CXCR 4 significantly attenuated stroke-enhanced NPC migration. ELISA analysis revealed that SDF-1alpha levels significantly increased (P<0.01) in the stroke hemisphere (43.6+/-6.5 pg/mg) when compared with the normal brain (25.2+/-1.9 pg/mg). Blind-well chamber assays showed that SDF-1alpha enhanced NPC migration in a dose-dependent manner with maximum migration at a dose of 500 ng/mL. In addition, SDF-1alpha induced directionally selective migration. These findings show that SDF-1alpha generated in the stroke hemisphere may guide NPC migration towards the ischemic boundary via binding to its receptor CXCR 4 in the NPC. Thus, our data indicate that SDF-1alpha/CXCR 4 is important for mediating specific migration of NPCs to the site of ischemic damaged neurons.
authors.affiliation: Henry Ford Hospital, Neurology Department, Detroit, Michigan, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Robin
authors.forename: Zheng G
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Rui L
authors.initials: RL
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Katakowski
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000378:metabolism; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D020521:Stroke / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4