PMID- 17061253 OWN - NLM STAT- MEDLINE DCOM- 20070313 LR - 20220825 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 84 IP - 8 DP - 2006 Dec TI - Modeling the neurovascular niche: VEGF- and BDNF-mediated cross-talk between neural stem cells and endothelial cells: an in vitro study. PG - 1656-68 AB - Neural stem cells (NSCs) exist in vascularized niches. Although there has been ample evidence supporting a role for endothelial cell-derived soluble factors as modulators of neural stem cell self-renewal and neuronal differentiation there is a paucity of data reported on neural stem cell modulation of endothelial cell behavior. We show that co-culture of NSCs with brain-derived endothelial cells (BECs) either in direct contact or separated by a porous membrane elicited robust vascular tube formation and maintenance, mediated by induction of vascular vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) and activation of vascular VEGFR2 and TrkB by NSC NO. Nitric oxide (NO) scavengers and sequestration of VEGF and BDNF blunted this induction of tube formation, whereas addition of exogenous NO donor, rBDNF and rVEGF rescued the induction of tube formation. Further, rBDNF enhanced NSC eNOS activation and NO generation, suggesting an inducible positive feed-back signaling loop between NSCs and BECs, providing for homeostasis and responsiveness of the resident NSCs and BECs comprising the neurovascular niche. These findings show the importance of reciprocal modulation of NSCs and BECs in induction and maintenance of the neurovascular niche and underscores their dynamic interactions. FAU - Li, Qi AU - Li Q AD - Department of Pathology, Yale University, School of Medicine, New Haven, CT 06520, USA. FAU - Ford, Millicent C AU - Ford MC FAU - Lavik, Erin B AU - Lavik EB FAU - Madri, Joseph A AU - Madri JA LA - eng GR - P01-NS35476/NS/NINDS NIH HHS/United States GR - R37-HL28373/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Tissue Proteins) RN - 0 (Platelet Endothelial Cell Adhesion Molecule-1) RN - 0 (Vascular Endothelial Growth Factor A) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Brain/cytology MH - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology MH - Cell Communication/*drug effects/physiology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Coculture Techniques/methods MH - Endothelial Cells/*drug effects/physiology/ultrastructure MH - Enzyme-Linked Immunosorbent Assay/methods MH - Green Fluorescent Proteins MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microscopy, Electron, Transmission/methods MH - Models, Biological MH - Nerve Tissue Proteins/metabolism MH - Neurons/*drug effects/physiology/ultrastructure MH - Nitric Oxide/metabolism MH - Platelet Endothelial Cell Adhesion Molecule-1/genetics MH - Stem Cells/*drug effects/physiology MH - Vascular Endothelial Growth Factor A/metabolism/*pharmacology EDAT- 2006/10/25 09:00 MHDA- 2007/03/14 09:00 CRDT- 2006/10/25 09:00 PHST- 2006/10/25 09:00 [pubmed] PHST- 2007/03/14 09:00 [medline] PHST- 2006/10/25 09:00 [entrez] AID - 10.1002/jnr.21087 [doi] PST - ppublish SO - J Neurosci Res. 2006 Dec;84(8):1656-68. doi: 10.1002/jnr.21087.