LincRNA-EPS in biomimetic vesicles targeting cerebral infarction promotes inflammatory resolution and neurogenesis

Abstract

Abstract 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.