Vascular Endothelial Cell-derived Exosomes Protect Neural Stem Cells Against Ischemia/reperfusion Injury

Abstract

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.

Keywords: brain protection; endothelial cells; exosomes; ischemic stroke; neural progenitor cells.