Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia

Abstract

The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site. Systemic administration of RVG-exosomes loaded with miR-124 promoted cortical neural progenitors to obtain neuronal identity and protect against ischemic injury by robust cortical neurogenesis. Our study suggests that RVG-exosomes can be utilized therapeutically for the targeted delivery of gene drugs to the brain, thus having great potential for clinical applications.

MiR‐27a‐3p and miR‐124‐3p, upregulated in endometrium and serum from women affected by Chronic Endometritis, are new potential molecular markers of endometrial receptivity

“…42 In addition, a paper on the miRNome of pregnancy in pigs detected miR-27a-3p as an important miRNA involved in maternal-fetal dialog. 45,46 Our data, supported by literature ev- In spite of the important upregulation of miR-124-3p and the downregulation of IL11 in the endometrium of women with CE, we did not find an anticorrelation ratio between mRNA and the miRNA. 44 MiR-124-3p was found downregulated in endometrial cancers and recently it has been demonstrated that modified exosomes could efficiently deliver miR-124-3p to the brain and that miRNAs are able to protect against ischemic injury by robust cortical neurogenesis.…”

“…44 MiR-124-3p was found downregulated in endometrial cancers and recently it has been demonstrated that modified exosomes could efficiently deliver miR-124-3p to the brain and that miRNAs are able to protect against ischemic injury by robust cortical neurogenesis. 45,46 We found the downregulation of IGF1 and IL11 and demonstrated the anticorrelation between miR-27a-3p and IGF1 (Figure 3).…”

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization

“…For transmission electron microscopy (TEM), purified exosomes from ADSCs were resuspended in PBS and imaged as detailed previously [26]. The proteins encapsulated into exosomes were analyzed by classical western blotting to test for the specific exosome markers CD9, CD63, CD81, and TSC101…”

“…Body temperature was monitored and maintained at 36.5 to 37.5 °C. A modified model of MCAO was used to create permanent focal ischemia, as previously described [26] . Briefly, the right middle cerebral artery (MCA) was occluded by inserting a monofilament nylon suture with a heat-rounded tip into the internal carotid artery, which was advanced further until it closed the origin of the MCA.…”

Exosomal microRNA and stroke: A review

“…49 Besides, after stroke cortical neurogenesis is increased by targeting exosomal miR-124. 71 In other words, deviant release of exosomal miRNAs results in alternating the gene expression which can give rise to the beginning and progress of cerebral ischemia reperfusion damages ( Table 1). miR-134 is known as a brain-specific miRNA, which is related to progression of dendritic and synaptic spine.…”