Fig. 5: EV administration induces angiogenesis and diminishes neuronal apoptosis in the mouse middle cerebral artery occlusion (MCAO) stroke model.

After exposing to 60 min of MCAO, mice were treated with PBS (MCAO control) or intravenously treated with EV administration at the beginning of the reperfusion and at 6 h later with another EV administration. A Quantitative analysis of TGF-β1, p-Smad2/3 and Smad2/3 expression in MCAO mice, MCAO mice treated with EVs and MCAO mice treated with si-EVs by Western blot analysis of the ischemic hemisphere. Western blot was normalized with the housekeeping protein β-actin (n = 5). B Quantitative analysis of proliferating cell (BrdU, red) rate in endothelial cells (CD31, green) of the ischemic striatum at post-MCAO day 7 by immunofluorescence staining in the aforementioned groups. EV administration increases the number of proliferating endothelial cells (BrdU+/CD31+) in the ischemic striatum compared with the si-EV group (n = 5). C Quantitative analysis of apoptotic cell (red) per mm² in the ischemic striatum at post-MCAO day 7 by TUNEL staining in the same groups (n = 5). Data are expressed as mean ± SD. **p < 0.01, ***p < 0.001, and ****p < 0.0001. EVs extracellular vesicles, MCAO middle cerebral artery occlusion, PBS phosphate-buffered saline, BrdU 5-bromo-2ʹ-deoxyuridine, TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling.