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
Axaron Bioscience AG, Heidelberg, Germany.
J Clin Invest. 2005 Aug;115(8):2083-98. doi: 10.1172/JCI23559. Epub 2005 Jul 7.
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.
粒细胞集落刺激因子（G-CSF）是一种强效造血因子，可提高髓系谱系细胞的存活率并驱动其分化，从而产生嗜中性粒细胞。在此，我们表明G-CSF可穿过完整的血脑屏障，并在两种不同的急性中风大鼠模型中减少梗死体积。G-CSF在成熟神经元中表现出强大的抗凋亡活性，并激活多种细胞存活途径。G-CSF及其受体在中枢神经系统的神经元中广泛表达，并且它们的表达受缺血诱导，这提示了一种自分泌保护信号机制。令人惊讶的是，G-CSF受体在成年神经干细胞中也有表达，并且G-CSF在体外可诱导神经元分化。G-CSF显著改善了皮质缺血后的长期行为结果，同时在体内刺激神经祖细胞反应，为功能恢复提供了联系。因此，G-CSF是中枢神经系统中的一种内源性配体，在对抗急性神经元变性和促进脑缺血后的长期可塑性方面均具有双重有益活性。因此，我们提出G-CSF作为中风和神经退行性疾病的一种潜在新药。
