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The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis

G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute st...

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Main Authors: Schneider, Armin (Author) , Krüger, Carola (Author) , Steigleder, Tobias (Author) , Weber, Daniela (Author) , Pitzer, Claudia (Author) , Laage, Rico (Author) , Aronowski, Jaroslaw (Author) , Maurer, Martin H. (Author) , Gaßler, Nikolaus (Author) , Mier, Walter (Author) , Hasselblatt, Martin (Author) , Kollmar, Rainer (Author) , Schwab, Stefan (Author) , Sommer, Clemens (Author) , Bach, Alfred (Author) , Kuhn, Hans-Georg (Author) , Schäbitz, Wolf-Rüdiger (Author)
Format: Article (Journal)
Language:English
Published: [August 2005]
In: The journal of clinical investigation
Year: 2005, Volume: 115, Issue: 8, Pages: 2083-2098
ISSN:1558-8238
DOI:10.1172/JCI23559
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1172/JCI23559
Verlag, lizenzpflichtig, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1172228/
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Author Notes:Armin Schneider, Carola Krüger, Tobias Steigleder, Daniela Weber, Claudia Pitzer, Rico Laage, Jaroslaw Aronowski, Martin H. Maurer, Nikolaus Gassler, Walter Mier, Martin Hasselblatt, Rainer Kollmar, Stefan Schwab, Clemens Sommer, Alfred Bach, Hans-Georg Kuhn, and Wolf-Rüdiger Schäbitz
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Summary:G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong antiapoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases.
Item Description:Gesehen am 28.05.2021
Physical Description:Online Resource
ISSN:1558-8238
DOI:10.1172/JCI23559

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