Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF
Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF
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DOI：
10.1016/j.bbi.2009.05.002
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发表时间：
2009-11-01
影响因子：
15.1
通讯作者：
Xiao, Bao-Guo
中科院分区：
文献类型：
--
作者：
Ding, Jing;Yu, Jie-Zhong;Xiao, Bao-Guo
Rho激酶（ROCK）是在细胞迁移、增殖和存活的基本过程中起重要作用的丝氨酸/苏氨酸激酶。阻断ROCK可促进轴突再生和神经保护，从而显示出临床应用于脊髓损伤和中风的治疗潜力。本研究以氧糖剥夺（OGD）为体外缺血模型，探讨ROCK抑制剂法舒地尔的神经保护和神经发生机制。法舒地尔刺激星形胶质细胞产生粒细胞集落刺激因子（G-CSF）。用法舒地尔（ACM-F）处理的星形胶质细胞条件培养基有助于神经球的产生，并减少神经元死亡。ACM-F中G-CSF的中和和神经元细胞培养物中G-CSF受体的阻断表明法舒地尔诱导的神经保护和/或神经发生部分通过星形胶质细胞衍生的G-CSF介导。我们的研究结果表明，ROCK抑制法舒地尔，保护神经元和动员神经干细胞，可能代表了一个有用的治疗前景，为各种神经系统疾病的特征是神经元死亡。(C)2009 Elsevier Inc. All rights reserved.
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.