Schaenzer, Anne and Wachs, Frank-Peter and Wilhelm, Daniel and Acker, Till and Cooper-Kuhn, Christiana and Beck, Heike and Winkler, Juergen and Aigner, Ludwig and Plate, Karl H. and Kuhn, H. Georg (2004) Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor. BRAIN PATHOLOGY, 14 (3). pp. 237-248. ISSN 1015-6305, 1750-3639
Full text not available from this repository. (Request a copy)Abstract
Hypoxia as well as global and focal ischemia are strong activators of neurogenesis in the adult mammalian central nervous system. Here we show that the hypoxia-inducible vascular endothelial growth factor (VEGF) and its receptor VEGFR-2/Flk-1 are expressed in clonally-derived adult rat neural stem cells in vitro. VEGF stimulated the expansion of neural stem cells whereas blockade of VEGFR-2/Flk-1-kinase activity reduced neural stem cell expansion. VEGF was also infused into the lateral ventricle to study changes in neurogenesis in the ventricle wall, olfactory bulb and hippocampus. Using a low dose (2.4 ng/d) to avoid endothelial proliferation and changes in vascular permeability, VEGF stimulated adult neurogenesis in vivo. After VEGF infusion, we observed reduced apoptosis but unaltered proliferation suggesting a survival promoting effect of VEGF in neural progenitor cells. Strong expression of VEGFR-2/Flk-1 was detected in the ventricle wall adjacent to the choroid plexus, a site of significant VEGF production, which suggests a paracrine function of endogenous VEGF on neural stem cells in vivo. We propose that VEGF acts as a trophic factor for neural stem cells in vitro and for sustained neurogenesis in the adult nervous system. These findings may have implications for the pathogenesis and therapy of neurodegenerative diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CENTRAL-NERVOUS-SYSTEM; RECEPTOR TYROSINE KINASE; MIDDLE CEREBRAL-ARTERY; LONG-TERM SURVIVAL; RAT-BRAIN; PERMEABILITY FACTOR; UP-REGULATION; FACTOR VEGF; HIPPOCAMPAL NEUROGENESIS; NEURONAL PROGENITORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Jul 2021 08:26 |
| Last Modified: | 07 Jul 2021 08:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37468 |
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