Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

作者：Mou Gao, Qin Dong, Dan Zou, Zhijun Yang, Lili Guo, Ruxiang Xu · 发表于：Neural Regeneration Research · 年份：2024 · DOI：10.4103/nrr.nrr-d-23-01495 · 被引用次数：4 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neurogenesis and neuroplasticity mechanisms、Inflammation biomarkers and pathways

JOURNAL/nrgr/04.03/01300535-202505000-00025/figure1/v/2024-07-28T173839Z/r/image-tiff Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair. We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling, influencing their activation such that they can promote neurological recovery. However, the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear. In this study, we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-α expression but suppressed insulin-like growth factor-1 expression. However, recombinant complement receptor 2-conjugated Crry (CR2-Crry) reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia, CXCL12, and tumor necrosis factor-α. Additionally, we observed that, in response to stimulation (including stimulation by CXCL12 secreted by activated microglia), CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4, Crry, and Akt signaling to modulate microglial activation. In agreement with these in vitro experimental results, we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,...