Intracerebral hemorrhage (ICH) is a common neurological disease, causing severe disability and even deaths. Stem cell transplantation has been increasingly used in stroke therapy, and neural stem cells (NSCs) are a good source for stem cell transplantation. However, the regulatory mechanism of NSCs remains unclear. In this study, we examined the impact of insulin-like growth factor-1 (IGF-1) secreted by NSCs on microglial polarization following ICH in adult C57BL/6 mice. Mouse models of ICH were established by collagenase injection. ICH mice received NSC transplantation 1 h after model establishment. Firstly, the changes of microglial polarization in cerebral tissues of ICH mice were detected by immunofluorescence and ELISA. Secondly, the molecular mechanism underlying the microglial polarization was evaluated repeatedly with the application of IGF-1R siRNA and IGF-1R-mediated inhibition. We assessed the brain water content and behavioral deficits of ICH mice 12, 24, 48, and 72 h after surgery. The survival of neurons in the brain was examined using Nissl staining and TUNEL staining at 72 h. The TLR4/NF-κB pathway implicated in ICH-induced inflammation was profiled by Western blot analysis and immunohistochemistry. Finally, the changes in microglia after ICH in mice were re-examined under different doses of rhIGF-1. In summary, NSC transplantation changed microglial polarization in ICH mice. IGF-1R inhibition and knockdown reversed the therapeutic effect of NSCs, and rhIGF-1 had an anti-inflammatory effect. The results of this study suggest that IGF-1R stimulation is a potential target for stem cell-based treatment of cerebral hemorrhage and may attenuate inflammatory response in the brain after bleeding.

脑出血（ICH）是一种常见的神经系统疾病，会导致严重的残疾甚至死亡。干细胞移植越来越多地用于中风治疗，神经干细胞（NSCs）是干细胞移植的良好来源。然而，NSCs的调控机制尚不清楚。在这项研究中，我们检查了 NSC 分泌的胰岛素样生长因子-1 (IGF-1) 对成年 C57BL/6 小鼠 ICH 后小胶质细胞极化的影响。通过胶原酶注射建立ICH小鼠模型。ICH小鼠在模型建立后1小时接受NSC移植。首先，通过免疫荧光和ELISA检测ICH小鼠脑组织中小胶质细胞极化的变化。其次，通过应用 IGF-1R siRNA 和 IGF-1R 介导的抑制，反复评估了小胶质细胞极化的分子机制。我们评估了 ICH 小鼠在手术后 12、24、48 和 72 小时的脑水含量和行为缺陷。在 72 小时时使用 Nissl 染色和 TUNEL 染色检查脑中神经元的存活情况。通过蛋白质印迹分析和免疫组织化学分析与 ICH 诱导的炎症有关的 TLR4/NF-κB 通路。最后，在不同剂量的rhIGF-1下重新检查小鼠ICH后小胶质细胞的变化。总之，NSC 移植改变了 ICH 小鼠的小胶质细胞极化。IGF-1R 抑制和敲低逆转了 NSCs 的治疗作用，而 rhIGF-1 具有抗炎作用。