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Background: Ischemic stroke is a severe acute cerebrovascular disease which can be improved with neuroprotective therapies at an early stage. However, due to the lack of effective neuroprotective drugs, most stroke patients have varying degrees of long-term disability. In the present study, we investigated the role of exosomes derived from CXCR4-overexpressing BMSCs in restoring vascular function and neural repair after ischemic cerebral infarction., Methods: BMSCs were transfected with lentivirus encoded by CXCR4 (BMSC CXCR4 ). Exosomes derived from BMSC CXCR4 (Exo CXCR4 ) were isolated and characterized by transmission electron microscopy and dynamic light scattering. Western blot and qPCR were used to analyze the expression of CXCR4 in BMSCs and exosomes. The acute middle cerebral artery occlusion (MCAO) model was prepared, Exo CXCR4 were injected into the rats, and behavioral changes were analyzed. The role of Exo CXCR4 in promoting the proliferation and tube formation for angiogenesis and protecting brain endothelial cells was determined in vitro ., Results: Compared with the control groups, the Exo CXCR4 group showed a significantly lower mNSS score at 7 d, 14 d, and 21 d after ischemia/reperfusion ( P < 0.05). The bEnd.3 cells in the Exo CXCR4 group have stronger proliferation ability than other groups ( P < 0.05), while the CXCR4 inhibitor can reduce this effect. Exosomes control (Exo Con ) can significantly promote the migration of bEnd.3 cells ( P < 0.05), while there was no significant difference between the Exo CXCR4 and Exo Con groups ( P > 0.05). Exo CXCR4 can further promote the proliferation and tube formation for the angiogenesis of the endothelium compared with Exo Con group ( P < 0.05). In addition, cobalt chloride (COCl2) can increase the expression of β -catenin and Wnt-3, while Exo Con can reduce the expression of these proteins ( P < 0.05). Exo CXCR4 can further attenuate the activation of Wnt-3a/ β -catenin pathway ( P < 0.05)., Conclusions: In ischemia/reperfusion injury, Exo CXCR4 promoted the proliferation and tube formation of microvascular endothelial cells and play an antiapoptotic role via the Wnt-3a/ β -catenin pathway., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 Xutong Li et al.)

Vascular endothelial cells were activated during acute ischemic brain injury, which could induce neural progenitor cell proliferation and migration. However, the mechanism was still unknown. In the current study, we explored whether vascular endothelial cells promoted neural progenitor cell proliferation and whether migration occurs via exosome communication. The acute middle cerebral artery occlusion (MCAO) model was prepared, and exosomes were isolated from bEnd.3 cells by ultracentrifugation. In the exosome injection (Exos) group and PBS injection (control) group, exosomes or PBS were injected intraventricularly into rats' brains 2 h after MCAO surgery, respectively. Sham group rats received the same surgical but did not cause middle cerebral artery occlusion. The infarct volume was reduced on day 21 after ischemic brain injury by MRI, and neurobehavioral outcomes were improved on day 7, 14, and 21 by exosome injection compared with the control (p < 0.05). On the 21st day after MCAO, the animals were euthanized, and the number of BrdU/nestin-positive cells was measured by immunofluorescence. BrdU/nestin-positive cells in Exos group rats were significantly increased (p < 0.05) in the peri infarct area, the ipsilateral DG zone of the hippocampus, and the ventral sub-regions of SVZ when compared with the rats in the control group. Further, in vitro study demonstrated that neural progenitor cell proliferation and migration were activated after exosomes treatment, and cell apoptosis was attenuated compared to the control (p < 0.05). Our study suggested that exosomes should be essential for the reconstruction of neuronal vascular units and brain protection in an acute ischemic injured brain., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Exosomes derived from the cerebral endothelial cells play essential roles in protecting neurons from hypoxia injury, but little is known regarding the biological effects and mechanisms of exosomes on brain plasticity. In this study, exosomes were isolated from rodent cerebral endothelial cells (bEnd.3 cells) by ultracentrifugation, either endothelial cell-derived exosomes (EC-Exo) or PBS was injected intraventricularly 2 h after the middle cerebral artery occlusion/reperfusion (MCAO/R) model surgery in the Exo group and control group, respectively. Sham group rats received the same surgical but not ischemic procedure. We evaluated the motor function of rats after MCAO/R, and the foot-fault rate of the Exo group was significantly lower than that of the control group within 23 days ( p < 0.05); the Catwalk analysis also showed gait difference between two groups ( p < 0.05). On day 28 after MCAO/R, we euthanized the rats, removed the motor cortex from the brain, and then sequenced the genes by using GO and KEGG to find transcriptome analysis of biological terms and functional annotations: The pathway enrichment revealed that the function of synaptic transmission, regulation of synaptic plasticity, and regulation of synaptic vesicle cycle was significantly enriched with the Exo group than control group. Furthermore, the upregulation of synapsin-I expression in the motor cortex ( p < 0.05) as well as the increase of the length of the dendrites were found in the Exo group ( p < 0.05) than the control group. We determined the content of exosome microRNA levels, and microRNA-126-3p was the highest (TPM) by transcriptome analysis. Moreover, the microRNA-126-3p protected PC12 cells from apoptosis and increased neurite outgrowth, illustrating the mechanism of how exosomes play a role in altering brain plasticity. This study demonstrated that EC-Exo promoted functional motor recovery in the MCAO/R model, exosomes were critical for the reconstruction of synaptic function in ischemic brain injury, and microRNA-126-3p from EC-Exo could serve as a treatment for nerve damage.