Osteopontin is a mediator of the lateral migration of neuroblasts from the subventricular zone after focal cerebral ischemia |
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| Institution: | 1. Department of Neurological Surgery, University of Wisconsin-Madison, WI 53792, United States;2. Neuroscience Training Program, University of Wisconsin-Madison, WI 53792, United States;3. Cardiovascular Research Center, University of Wisconsin-Madison, WI 53792, United States;1. The School for Engineering of Matter, Transport and Energy (SEMTE), Arizona State University, 501 E. Tyler Mall, Tempe, AZ 85287-9809, United States;2. Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, 156 Fitzpatrick Hall, Notre Dame, IN 46556-5637, United States;3. Department of Mathematics, University College London, Gower Street, London WC1E 6BT, United Kingdom;4. School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ 85287-1804, United States;1. Department of Biological Sciences, Boise State University, Boise, ID 83725, USA;2. Biomolecular Ph.D. program, Boise State University, Boise, ID 83725, USA;1. Virginia Tech Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, USA;2. Department of Biological Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA;3. Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA;4. Office of the University Veterinarian & Animal Resources, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA;1. Department of Biological Sciences, Clemson University, Clemson, SC 29634-0314, USA |
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| Abstract: | We and others have shown that focal cerebral ischemia induces lateral migration of neuroblasts from the ipsilateral subventricular zone (SVZ) to the ischemic striatum. The signaling pathways underlying this phenomenon are not fully understood. The present study examined the role of osteopontin (OPN) in post-ischemic lateral migration of neuroblasts. Focal ischemia was induced by transient middle cerebral artery occlusion in adult spontaneous hypertensive rats. The expression of OPN in the ischemic brain was evaluated by immunohistochemistry, which showed that an up-regulation of OPN expression in the ipsilateral striatum at day 3, 7, 14 and 1 month of reperfusion with a peak at day 7. Double staining showed co-localization of OPN with ED1+ macrophages/microglia in the ischemic regions. Inhibition of OPN activity by infusing a neutralizing antibody against OPN into the ischemic striatum significantly decreased the area covered with doublecortin+ neuroblasts in the ipsilateral striatum. In vitro, OPN treatment did not affect the proliferation of neural progenitors, but induced an increased trans-well and radial migration of neural progenitors. The cultured neural progenitors expressed the OPN receptors CD44 and integrin β1. Blockade of the CD44 receptor had no effects on OPN mediated trans-well and radial migration of neural progenitors. However, blockade of integrin β1 receptor abolished the migration of neural progenitors in the absence or the presence of OPN. These results suggest that up-regulated expression of OPN produced by macrophages/microglia in the ischemic brain is an attractant and inducer for the lateral migration of neuroblasts from the SVZ to the injured region. |
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