MiR-145 enriched exosomes derived from bone marrow-derived mesenchymal stem cells protects against cerebral ischemia-reperfusion injury through downregulation of FOXO1

Background: Mesenchymal stem cells-derived exosomes (MSCs-Exo) were able to exert neuroprotective effects in brain injury after ischemic stroke (IS). In addition, exosomes containing microRNAs (miRNAs) can be transported to recipient cells to mediate intercellular communication. It has been shown that the level of miR-145 was significantly downregulated in brain tissues of rats subjected to middle cerebral artery occlusion (MCAO). However, the role of MSCs-derived exosomal miR-145 in IS progression remains largely unknown.Methods: Microglial BV2 cell exposed to oxygen-glucose deprivation/reperfusion (OGD/R) was applied to mimic cerebral ischemia/reperfusion (I/R) injury conditions in vitro. In addition, a rat model of MCAO was established to induce I/R injury. Meanwhile, exosomes were isolated from miR-145-transfected bone marrow MSCs, and then these isolated exosomes were used to treat OGD/R-stimulated BV-2 cell and rats subject to MCAO/R.Results: In this study, we found that miR-145 could be transferred from MSCs to BV2 cells via exosomes. In addition, exosomal miR-145-derived from MSCs was able to shift microglia polarization toward anti-inflammatory M2 phenotype in OGD/R-stimulated BV2 cells. Moreover, exosomal miR-145 markedly suppressed the apoptosis, cell cycle arrest and oxidative stress in OGD/R-treated BV2 cells. Additionally, exosomal miR-145 notably decreased the expression of FOXO1 in BV2 cell exposed to OGD/R and in brain tissues of MCAO rats. Furthermore, exosomal miR-145 remarkably decreased infarct area in MCAO rats.Conclusion: Collectively, exosomal miR-145-derived from MSCs was able to attenuate cerebral I/R injury through downregulation of FOXO1. These studies may serve as a potential approach for treating of ce-rebral I/R injury. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

The study demonstrates that exosomal miR-145 derived from MSCs can attenuate cerebral ischemia/reperfusion injury by downregulating FOXO1, leading to a shift in microglial polarization and inhibition of apoptosis, cell cycle arrest, and oxidative stress. Exosomal miR-145 may serve as a potential therapeutic approach for treating cerebral ischemia/reperfusion injury.