Figure 8.

EV administration protects against ischemia-induced brain damage in mice. (A-B) To evaluate perivascular CSF penetration into the brain parenchyma, 10 μL of fluorescent CSF tracer were injected intracisternally into sham, MCAO + PBS, and MCAO + EVs mice. Thirty min after injection, the periinfarct fluorescence was measured. Representative images indicate that compared to sham brains, CSF tracer penetration into MCAO brains was markedly slowed. However, CSF tracer penetration was dramatically increased in MCAO + EVs mice compared to MCAO + PBS mice (n = 3-5). (C-E) Statistical analysis of laser speckle perfusion results in mice. Cerebral perfusion in the contralateral cortex is comparable among the untreated MCAO mice and MCAO mice treated with EVs on day 7 after stroke. The EV-treated mice were associated with a higher ipsilateral cortex blood flow and value of ipsilateral ratio to contralateral cortex blood flow (n = 8). (F) Statistical results of mouse brain water content between the untreated MCAO mice and MCAO mice treated with EVs (n = 9). (G-L) EV delivery protects against ischemia-induced motor coordination impairment. The rotarod test, the tightrope test, the balance beam test, the paw slips recording, the corner turn test, and the modified neurological severity scores were tested on day 1 before the stroke and day 7 after the stroke (n = 4-9). *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001; NS, not statistically significant; EVs, extracellular vesicles; MCAO, middle cerebral artery occlusion.