Transplantation of curcumin-activated olfactory ensheathing cells (aOECs) improved functional recovery in spinal cord injury (SCI) rats. Nevertheless, little is known considering the underlying mechanisms. At the present study, we investigated the promotion of regeneration and functional recovery after transplantation of aOECs into rats with SCI and the possible underlying molecular mechanisms. Primary OECs were prepared from the olfactory bulb of rats, followed by treatment with 1µM CCM at 7–10 days of culture, resulting in cell activation. Concomitantly, rat SCI model was developed to evaluate the effects of transplantation of aOECs in vivo. Subsequently, microglia were isolated, stimulated with 100 ng/mL lipopolysaccharide (LPS) for 24 h to polarize to M1 phenotype and treated by aOECs conditional medium (aOECs-CM) and OECs conditional medium (OECs-CM), respectively. Changes in the expression of pro-inflammatory and anti-inflammatory phenotypic markers expression were detected using western blotting and immunofluorescence staining, respectively. Finally, a series of molecular biological experiments including knock-down of triggering receptor expressed on myeloid cells 2 (TREM2) and analysis of the level of apolipoprotein E (APOE) expression were performed to investigate the underlying mechanism of involvement of CCM-activated OECs in modulating microglia polarization, leading to neural regeneration and function recovery. CCM-activated OECs effectively attenuated deleterious inflammation by regulating microglia polarization from the pro-inflammatory (M1) to anti-inflammatory (M2) phenotype in SCI rats and facilitated functional recovery after SCI. In addition, microglial polarization to M2 elicited by aOECs-CM in LPS-induced microglia was effectively reversed when TREM2 expression was downregulated. More importantly, the in vitro findings indicated that aOECs-CM potentiating LPS-induced microglial polarization to M2 was partially mediated by the TREM2/nuclear factor kappa beta (NF-κB) signaling pathway. Besides, the expression of APOE significantly increased in CCM-treated OECs. CCM-activated OECs could alleviate inflammation after SCI by switching microglial polarization from M1 to M2, which was likely mediated by the APOE/TREM2/NF-κB pathway, and thus ameliorated neurological function. Therefore, the present finding is of paramount significance to enrich the understanding of underlying molecular mechanism of aOECs-based therapy and provide a novel therapeutic approach for treatment of SCI.

移植姜黄素激活的嗅鞘细胞（aOEC）可改善脊髓损伤（SCI）大鼠的功能恢复。然而，考虑到潜在的机制，人们知之甚少。在本研究中，我们研究了aOECs移植到SCI大鼠体内后对再生和功能恢复的促进作用以及可能的分子机制。从大鼠嗅球中制备原代 OEC，然后在培养 7-10 天时用 1μM CCM 处理，导致细胞活化。同时，建立了大鼠SCI模型来评估aOECs体内移植的效果。随后，分离小胶质细胞，用100 ng/mL脂多糖（LPS）刺激24小时以极化至M1表型，并分别用aOECs条件培养基（aOECs-CM）和OECs条件培养基（OECs-CM）处理。分别使用蛋白质印迹和免疫荧光染色检测促炎和抗炎表型标志物表达的变化。最后，进行了一系列分子生物学实验，包括敲低髓样细胞表达的触发受体2（TREM2）和分析载脂蛋白E（APOE）表达水平，以研究CCM激活的OEC参与的潜在机制。调节小胶质细胞极化，导致神经再生和功能恢复。CCM 激活的 OEC 通过调节 SCI 大鼠中小胶质细胞从促炎 (M1) 到抗炎 (M2) 表型的极化，有效减轻有害炎症，并促进 SCI 后的功能恢复。此外，当 TREM2 表达下调时，LPS 诱导的小胶质细胞中 aOECs-CM 诱导的小胶质细胞极化至 M2 被有效逆转。更重要的是，体外研究结果表明，aOECs-CM 增强 LPS 诱导的小胶质细胞极化至 M2 的作用部分是由 TREM2/核因子 kappa beta (NF-κB) 信号通路介导的。此外，CCM处理的OECs中APOE的表达显着增加。CCM 激活的 OEC 可以通过将小胶质细胞极化从 M1 切换到 M2 来减轻 SCI 后的炎症，这可能是由 APOE/TREM2/NF-κB 通路介导的，从而改善神经功能。因此，本研究结果对于丰富对基于aOECs的治疗的潜在分子机制的理解并为SCI的治疗提供新的治疗方法具有重要意义。