Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 23, Issue 8, Pages 1083-1088Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2009.05.002
Keywords
Fasudil; Rho kinase inhibitor; Oxygen-glucose deprivation; Astrocytes; Granulocyte colony-stimulating factor
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Funding
- National Natural Science Foundation of China [30572164]
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Rho-kinases (ROCK) are serine/threonine kinases that play an important role in fundamental processes of cell migration, proliferation and survival. Blockade of ROCK promotes axonal regeneration and neuroprotection, thereby exhibiting therapeutic potentials for clinical application to spinal cord damage and stroke. Here we explored the mechanisms of Fasudil, a ROCK inhibitor, in neuroprotection and neurogenesis by using oxygen-glucose deprivation (OGD) as an in vitro ischemia model. Fasudil stimulates astrocytes to produce granulocyte colony-stimulating factor (G-CSF). Astrocyte-conditioned medium treated with Fasudil (ACM-F) contributes to the generation of neurospheres, and decreases neuron death. Neutralization of G-CSF in ACM-F and blocking of G-CSF receptor in neuronal cell cultures revealed that Fasudil-induced neuroprotection and/or neurogenesis are mediated partially through astrocyte-derived G-CSF. Our results indicate that ROCK inhibition by Fasudil, protecting neurons and mobilizating neural stem cells, might represent a useful therapeutic perspective for various neurological disorders characterized by neuron death. (C) 2009 Elsevier Inc. All rights reserved.
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