Jeffrey M. Rosenstein, Ph.D.
Professor of Anatomy and Regenerative Biology and of Neurological Surgery

Address The George Washington University School of Medicine and Health Sciences 2300 I Street NW, Ross Hall 211 Washington, DC 20037 Tel: 202-994-3169 Fax: 202-994-8885 Email: anajmr@gwumc.edu

The subependymal zone (SEZ) of the adult rodent forebrain borders the lateral ventricles and contains neural (and glial) progenitor cells that proliferate throughout life and migrate to the olfactory bulb where they become interneurons. Our preliminary data indicate that chronic intrastriatal infusion of vascular endothelial growth factor (VEGF), known primarily as an angiogenic factor, has strong effects on the adult SEZ where it causes increased cell division, increased vascular permeability and the surprising upregulation of the VEGF flk-1 receptor which is present on developing neurons. VEGF may have heretofore unknown growth promoting effects on this highly significant region. We already have shown that adult solid SEZ survives direct transplantation into the brain without any growth factor enhancement. The application of VEGF in vivo or in vitro prior to grafting may provide an impetus for enhanced neuronal phenotypic expression and growth via direct interactions with progenitor cells and/or by increased vascularization.

Our research is designed to determine if: 1) VEGF administration to the SEZ in situ will stimulate an increase in the neuronal population and 2) if VEGF application to the SEZ in vitro enhances the neuronal phenotype. We plan to do further experiments to determine a mechanistic role for VEGF application by examining VEGF receptor mediation and beginning to understand VEGF signaling pathways in CNS angiogenesis, permeability and neuritic growth. Pre-treatment of SEZ grafts with VEGF, both in situ and in vitro, may augment neuronal growth and survival directly via stem/progenitor flk-1 expression or indirectly by increased vascularization. These studies will attempt to determine the cell biological underpinnings of how VEGF may affect vascular and neuronal aspects of SEZ tissue. Understanding such basic cell biological issues could be of great benefit for producing improved stem/progenitor cell survival and growth.

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PubMed Publications