Stanford University, Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA 94305-5454, USA.
Brain Behav Immun. 2013 May;30:33-44. doi: 10.1016/j.bbi.2012.09.010. Epub 2012 Oct 3.
Cranial irradiation for the treatment of brain tumors causes a delayed and progressive cognitive decline that is pronounced in young patients. Dysregulation of neural stem and progenitor cells is thought to contribute to these effects by altering early childhood brain development. Earlier work has shown that irradiation creates a chronic neuroinflammatory state that severely and selectively impairs postnatal and adult neurogenesis. Here we show that irradiation induces a transient non-classical cytokine response with selective upregulation of CCL2/monocyte chemoattractant protein-1 (MCP-1). Absence of CCL2 signaling in the hours after irradiation is alone sufficient to attenuate chronic microglia activation and allow the recovery of neurogenesis in the weeks following irradiation. This identifies CCL2 signaling as a potential clinical target for moderating the long-term defects in neural stem cell function following cranial radiation in children.
颅部放疗治疗脑肿瘤会导致延迟和进行性认知能力下降，在年轻患者中更为明显。神经干细胞和祖细胞的失调被认为通过改变儿童早期大脑发育而促成这些影响。早期的工作表明，放疗会产生慢性神经炎症状态，严重且选择性地损害出生后和成年时期的神经发生。在这里，我们表明放疗会诱导一种短暂的非经典细胞因子反应，选择性地上调 CCL2/单核细胞趋化蛋白-1（MCP-1）。在放疗后数小时内缺乏 CCL2 信号足以减弱慢性小胶质细胞激活，并允许在放疗后数周内神经发生的恢复。这表明 CCL2 信号作为一种潜在的临床靶点，可以调节儿童颅部放疗后神经干细胞功能的长期缺陷。
