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The Journal of Neuroscience, December 13, 2006, 26(50):13007-13016; doi:10.1523/JNEUROSCI.4323-06.2006
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Development/Plasticity/Repair
A Neurovascular Niche for Neurogenesis after Stroke
John J. Ohab,1 Sheila Fleming,1 Armin Blesch,2 andS. Thomas Carmichael1 1Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095-1735, and 2Department of Neuroscience, University of California, San Diego, La Jolla, California 92093-0626
Correspondence should be addressed to Dr. S. Thomas Carmichael, Department of Neurology, Geffen School of Medicine at University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095. Email: scarmichael{at}mednet.ucla.edu
Stroke causes cell death but also birth and migration of new neurons within sites of ischemic damage. The cellular environment that induces neuronal regeneration and migration after stroke has not been defined. We have used a model of long-distance migration of newly born neurons from the subventricular zone to cortex after stroke to define the cellular cues that induce neuronal regeneration after CNS injury. Mitotic, genetic, and viral labeling and chemokine/growth factor gain- and loss-of-function studies show that stroke induces neurogenesis from a GFAP-expressing progenitor cell in the subventricular zone and migration of newly born neurons into a unique neurovascular niche in peri-infarct cortex. Within this neurovascular niche, newly born, immature neurons closely associate with the remodeling vasculature. Neurogenesis and angiogenesis are causally linked through vascular production of stromal-derived factor 1 (SDF1) and angiopoietin 1 (Ang1). Furthermore, SDF1 and Ang1 promote post-stroke neuroblast migration and behavioral recovery. These experiments define a novel brain environment for neuronal regeneration after stroke and identify molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury.
Key words: regeneration; neurovascular coupling; hypoxia–ischemia; neurogenesis; stem cells; functional recovery
Received July 24, 2006; revised Nov. 6, 2006; accepted Nov. 7, 2006.
Correspondence should be addressed to Dr. S. Thomas Carmichael, Department of Neurology, Geffen School of Medicine at University of California, Los Angeles, 710 Westwood Plaza, Los Angeles, CA 90095. Email: scarmichael{at}mednet.ucla.edu
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