BACKGROUND Inflammatory damage following stroke aggravates brain damage, resulting in long-term neurological sequelae. The purpose of this study was to identify ways to reduce inflammatory reactions and to accelerate neuron regeneration after cerebral apoplexy. METHODS We formulated a biomimetic vesicle, the leukosome, constituted by liposome, artificial long intergenic noncoding RNA (lincRNA)-EPS, and membrane proteins derived from macrophages and their physical-chemical characteristics were evaluated. Migration distance and cytotoxic levels were measured to determine the effect of lncEPS-leukosomes on lipopolysaccharide-activated microglia. An in vivo transient middle cerebral artery occlusion/reperfusion (tMCAO) model was established in mice, which were treated with lncEPS-leukosomes. Vesicle seepage, infiltration of inflammatory cells, cytotoxic levels in the cerebrospinal fluid, and neural stem cell (NSC) density were measured. RESULTS Biomimetic vesicles with a homogeneous size increased lincRNA-EPS levels in activated microglia by 77.9%. In vitro studies showed that lincRNA-EPS inhibited the migration and cytotoxic levels of activated microglia by 63.2% and 43.6%, respectively, which promoted NSC proliferation and anti-apoptotic ability. In vivo data showed that leukosomes targeted to inflamed sites and lncEPS-leukosomes decreased the infiltration of inflammatory cells and cytotoxic levels by 81.3% and 48.7%, respectively. In addition, lncEPS-leukosomes improved neuron density in the ischemic core and boundary zone after tMCAO. CONCLUSIONS The biomimetic vesicles formulated in this study targeted inflammatory cells and accelerated neuron regeneration by promoting inflammation resolution. This study may provide a promising treatment approach for accelerated neuron regeneration after cerebral apoplexy.

中文翻译：

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靶向脑梗死的仿生囊泡中的LincRNA-EPS促进炎症消退和神经发生。

背景技术中风后的炎性损害加重了脑损害，导致长期的神经系统后遗症。这项研究的目的是确定减少脑中风后炎症反应和加速神经元再生的方法。方法我们制备了由脂质体，人工长基因间非编码RNA（lincRNA）-EPS组成的仿生囊泡，白细胞，并评估了来自巨噬细胞的膜蛋白及其理化特性。测量迁移距离和细胞毒性水平，以确定lncEPS-白体对脂多糖激活的小胶质细胞的作用。在小鼠中建立了体内瞬时脑中动脉闭塞/再灌注（tMCAO）模型，并用lncEPS-白体处理。囊泡渗漏，炎性细胞浸润，测量脑脊液中的细胞毒性水平和神经干细胞（NSC）密度。结果具有均一大小的仿生囊泡使活化小胶质细胞中的lincRNA-EPS水平增加了77.9％。体外研究表明，lncRNA-EPS分别抑制了活化的小胶质细胞的迁移和细胞毒性水平，分别为63.2％和43.6％，从而促进了NSC的增殖和抗凋亡能力。体内数据显示，靶向发炎部位的白细胞和lncEPS-白体分别使炎性细胞浸润和细胞毒性水平降低了81.3％和48.7％。此外，lncEPS-白体可改善tMCAO后缺血核心和边界区的神经元密度。结论本研究中拟定的仿生囊泡可通过促进炎症消融来靶向炎症细胞并加速神经元再生。这项研究可能为脑卒中后加速神经元再生提供有希望的治疗方法。