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(Stroke. 2007;38:3032.)
© 2007 American Heart Association, Inc.

Original Contributions

Long-Term Neuroblast Migration Along Blood Vessels in an Area With Transient Angiogenesis and Increased Vascularization After Stroke

Pär Thored, PhD; James Wood, BSc; Andreas Arvidsson, MD, PhD; Jörg Cammenga, MD, PhD; Zaal Kokaia, PhD Olle Lindvall, MD, PhD

From Laboratory of Neurogenesis and Cell Therapy (P.T., J.W., A.A., O.L.), Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden; Laboratory of Gene Therapy and Molecular Medicine (J.C.), Wallenberg Neuroscience Center, University Hospital, Lund, Sweden; Laboratory of Neural Stem Cell Biology (Z.K.), Section of Restorative Neurology, University Hospital, Lund, Sweden; Lund Strategic Research Center for Stem Cell Biology and Cell Therapy (P.T., J.W., A.A., J.C., Z.K., O.L.), Lund, Sweden.

Correspondence to Olle Lindvall, Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden. E-mail olle.lindvall{at}med.lu.se

Background and Purpose— Stroke induced by middle cerebral artery occlusion (MCAO) causes long-term formation of new striatal neurons from stem/progenitor cells in the subventricular zone (SVZ). We explored whether MCAO leads to hypoxia, changes in vessel density, and angiogenesis in the ipsilateral SVZ and adjacent striatum, and determined the relation between the migrating neuroblasts and the vasculature.

Methods— Adult rats were subjected to 2 hours of MCAO. Hypoxia was studied by injecting Hypoxyprobe-1 during MCAO or 6 weeks later. Vessel density and length was estimated using stereology. New cells were labeled with 5'-bromo-2'deoxyuridine (BrdU) during weeks 1 and 2 or 7 and 8 after MCAO, and angiogenesis was assessed immunohistochemically with antibodies against BrdU and endothelial cell markers. Distance from neuroblasts to nearest vessel was measured using confocal microscopy.

Results— The ischemic insult caused transient hypoxia and early, low-grade angiogenesis, but no damage or increase of vascular density in the SVZ. Angiogenesis was detected during the first 2 weeks in the dorsomedial striatum adjacent to the SVZ, which also showed long-lasting increase of vascularization. At 2, 6, and 16 weeks after MCAO, the majority of neuroblasts migrated through this area toward the damage, closely associated with blood vessels.

Conclusions— The vasculature plays an important role for long-term striatal neurogenesis after stroke. During several months, neuroblasts migrate close to blood vessels through an area exhibiting early vascular remodeling and persistently increased vessel density. Optimizing vascularization should be an important strategy to promote neurogenesis and repair after stroke.

Key Words: angiogenesis • hypoxia • neurogenesis • stroke

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