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- Calvo, Charles-Félix, et al.
(författare)
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Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis.
- 2011
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Ingår i: Genes & Development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- Neural stem cells (NSCs) are slowly dividing astrocytes that are intimately associated with capillary endothelial cells in the subventricular zone (SVZ) of the brain. Functionally, members of the vascular endothelial growth factor (VEGF) family can stimulate neurogenesis as well as angiogenesis, but it has been unclear whether they act directly via VEGF receptors (VEGFRs) expressed by neural cells, or indirectly via the release of growth factors from angiogenic capillaries. Here, we show that VEGFR-3, a receptor required for lymphangiogenesis, is expressed by NSCs and is directly required for neurogenesis. Vegfr3:YFP reporter mice show VEGFR-3 expression in multipotent NSCs, which are capable of self-renewal and are activated by the VEGFR-3 ligand VEGF-C in vitro. Overexpression of VEGF-C stimulates VEGFR-3-expressing NSCs and neurogenesis in the SVZ without affecting angiogenesis. Conversely, conditional deletion of Vegfr3 in neural cells, inducible deletion in subventricular astrocytes, and blocking of VEGFR-3 signaling with antibodies reduce SVZ neurogenesis. Therefore, VEGF-C/VEGFR-3 signaling acts directly on NSCs and regulates adult neurogenesis, opening potential approaches for treatment of neurodegenerative diseases.
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| 2. |
- Rolfs, Arndt, et al.
(författare)
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Protocol and Methodology of the Stroke in Young Fabry Patients (sifap1) Study: A Prospective Multicenter European Study of 5,024 Young Stroke Patients Aged 18-55 Years
- 2011
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Ingår i: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 31:3, s. 253-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients. Methods: We initiated the Stroke in Young Fabry Patients (sifap1) study as a multinational prospective European study of stroke patients aged 18-55 years and collected a broad range of clinical, laboratory, and radiological data using stringent standardized methods. All patients were tested for Fabry disease and blood was stored for future genetic testing. Results: We managed to enroll 5,024 eligible young stroke patients in 15 countries and 47 centers across Europe between April 2007 and January 2010. The median number of patients included per center was 98 with a range between 8 and 315. The average duration of patient recruitment per center was 22 months, ranging between 5 and 33 months. The database was closed in July 2010. This paper describes protocol and methodology of the sifap1 study. Conclusion: The sifap1 study included the largest series of young stroke patients so far and will allow for analyses on a large number of aspects of stroke in the young. Copyright (C) 2010 S. Karger AG, Basel
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