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- Title
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis.
- Authors
Schneider, Armin; Krüger, Carola; Steigleder, Tobias; Weber, Daniela; Pitzer, Claudia; Laage, Rico; Aronowski, Jaroslaw; Maurer, Martin H; Gassler, Nikolaus; Mier, Walter; Hasselblatt, Martin; Kollmar, Rainer; Schwab, Stefan; Sommer, Clemens; Bach, Alfred; Kuhn, Hans-Georg; Schäbitz, Wolf-Rüdiger
- Abstract
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 anti-apoptotic 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.
- Publication
The Journal of clinical investigation, 2005, Vol 115, Issue 8, p2083
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI23559