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First published online October 6, 2005
Stem Cells Vol. 24 No. 3 March 2006, pp. 739 -747
doi:10.1634/stemcells.2005-0281; www.StemCells.com
© 2006 AlphaMed Press

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TISSUE-SPECIFIC STEM CELLS

Persistent Production of Neurons from Adult Brain Stem Cells During Recovery after Stroke

Pär Thoreda,c, Andreas Arvidssona,c, Emanuele Caccib,c, Henrik Ahleniusb,c, Therése Kallurb,c, Vladimer Darsaliab,c, Christine T. Ekdahla,c, Zaal Kokaiab,c, Olle Lindvalla,c

a Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden;
b Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, Stem Cell Institute, University Hospital, Lund, Sweden;
c Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund, Sweden

Key Words. Stem cells • Neurogenesis • Striatum • Stroke

Correspondence: Olle Lindvall, M.D., Ph.D., Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden. Telephone: 46-46-222 0543; Fax: 46-46-222 0560; e-mail: olle.lindvall{at}med.lu.se

Received June 23, 2005; accepted for publication September 27, 2005.
Neural stem cells in the subventricular zone of adult rodents produce new striatal neurons that may replace those that have died after stroke; however, the neurogenic response has been considered acute and transient, yielding only small numbers of neurons. In contrast, we show herein that striatal neuroblasts are generated without decline at least for 4 months after stroke in adult rats. Neuroblasts formed early or late after stroke either differentiate into mature neurons, which survive for several months, or die through caspase-mediated apoptosis. The directed migration of the new neurons toward the ischemic damage is regulated by stromal cell-derived factor-1{alpha} and its receptor CXCR4. These results show that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self-repair strategies to improve recovery after stroke.




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