naa a22 4500 510776299 CHVBK 20180411083231.0 cr unu---uuuuu 180411e20130401xx s 000 0 eng 10.1007/s12975-012-0213-6 doi (NATIONALLICENCE)springer-10.1007/s12975-012-0213-6 Vascular Endothelial Growth Factors A and C are Induced in the SVZ Following Neonatal Hypoxia-Ischemia and Exert Different Effects on Neonatal Glial Progenitors [Elektronische Daten] [Jennifer Bain, Lisamarie Moore, Zhihua Ren, Sophia Simonishvili, Steven Levison] Episodes of neonatal hypoxia-ischemia (H-I) are strongly associated with cerebral palsy and a wide spectrum of other neurological deficits in children. Two key processes required to repair damaged organs are to amplify the number of precursors capable of regenerating damaged cells and to direct their differentiation towards the cell types that need to be replaced. Since hypoxia induces vascular endothelial growth factor (VEGF) production, it is logical to predict that VEGFs are key mediators of tissue repair after H-I injury. The goal of this study was to test the hypothesis that certain VEGF isoforms increase during recovery from neonatal H-I and that they would differentially affect the proliferation and differentiation of subventricular zone (SVZ) progenitors. During the acute recovery period from H-I, both VEGF-A and VEGF-C were transiently induced in the SVZ, which correlated with an increase in SVZ blood vessel diameter. These growth factors were produced by glial progenitors, astrocytes, and to a lesser extent, microglia. VEGF-A promoted the production of astrocytes from SVZ glial progenitors, while VEGF-C stimulated the proliferation of both early and late oligodendrocyte progenitor cells (OPCs), which was abolished by blocking VEGFR-3. Altogether, these results provide new insights into the signals that coordinate the reactive responses of the progenitors in the SVZ to neonatal H-I. Our studies further suggest that therapeutics that can extend VEGF-C production and/or agonists that stimulate VEGFR-3 will promote OPC development to enhance myelination after perinatal brain injury. Springer Science+Business Media, LLC, 2012 Neonatal hypoxia-ischemia nationallicence Subventricular zone nationallicence Glial progenitor nationallicence Oligodendrocyte nationallicence Astrocyte nationallicence Vascular endothelial growth factor nationallicence Cytokine nationallicence Bain Jennifer Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut Moore Lisamarie Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut Ren Zhihua Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut Simonishvili Sophia Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut Levison Steven Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 158-170 1868-4483 4:2<158 2013 4 12975 https://doi.org/10.1007/s12975-012-0213-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12975-012-0213-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bain Jennifer Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut NATIONALLICENCE 700 1- Moore Lisamarie Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut NATIONALLICENCE 700 1- Ren Zhihua Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut NATIONALLICENCE 700 1- Simonishvili Sophia Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut NATIONALLICENCE 700 1- Levison Steven Department of Neurology and Neurosciences, UMDNJ—New Jersey Medical School, 07103, Newark, NJ, USA aut NATIONALLICENCE 773 0- Translational Stroke Research Springer-Verlag 4/2(2013-04-01), 158-170 1868-4483 4:2<158 2013 4 12975 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer