1. ¹Henry Ford Hospital, Neurology Department, Detroit, Michigan, USA
2. ²Oakland University, Physics Department, Rochester, Michigan, USA

Correspondence: Dr M Chopp, Neurology Research Building, Room 3056, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, Detroit, MI 48202, USA. E-mail: chopp@neuro.hfh.edu

Received 30 March 2005; Revised 22 April 2005; Accepted 17 May 2005; Published online 15 June 2005.

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 1 (SDF-1) 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 (67.225.2 m) compared with the migration on normal brain slices (29.529.5 m). Immunohistochemistry showed that CXCR 4, a receptor of SDF-1, is expressed in the NPCs and migrating neuroblasts in stroke brain. Blocking SDF-1 by a neutralizing antibody against CXCR 4 significantly attenuated stroke-enhanced NPC migration. ELISA analysis revealed that SDF-1 levels significantly increased (P<0.01) in the stroke hemisphere (43.66.5 pg/mg) when compared with the normal brain (25.21.9 pg/mg). Blind-well chamber assays showed that SDF-1 enhanced NPC migration in a dose-dependent manner with maximum migration at a dose of 500 ng/mL. In addition, SDF-1 induced directionally selective migration. These findings show that SDF-1 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-1/CXCR 4 is important for mediating specific migration of NPCs to the site of ischemic damaged neurons.