Abstract

Objective: To assess the therapeutic effects and underlying mechanisms of exogenous exosomes derived from RIC in improving post-resuscitation neurologic dysfunction in a rat model of CA. Methods: Exogenous exosomes were isolated from the plasma of healthy adult male Sprague-Dawley rats that underwent RIC.36 adult male SD rats were randomly assigned to three groups: 1) Sham, 2) Control, or 3) Exosome. The control and exosome groups underwent 7 minutes of asphyxia-induced cardiac arrest. Five minutes after the ROSC, either exosome (1х10 10 Particles) or placebo (normal saline) were administered via intravenous infusion. Neurological outcomes were assessed using the neuropsychological deficit score (NDS), open field test, Y maze, and Morris Water Maze. Levels of plasma hyaluronic acid (HA) and syndecan-1 (Sdc-1) were measured to evaluate the degree of endothelium glycocalyx degradation. Results: Compared with Sham group, the Control group showed significant neurological dysfunction after ROSC. Compared to the control group, the exosome group exhibited significantly better performance in the open field, Y maze experiments and Morris water maze ( p < 0.05). Compared with the Sham group, the plasma levels of HA and Sdc-1 in the Control group were significantly increased 24 hours after ROSC (P<0.05), while the plasma levels of HA and Sdc-1 in the Exosome group were significantly lower than those in the Control group(P<0.05). Conclusions: Exosomes derived from RIC have been shown to be effective in improving neurological dysfunction following cardiac arrest. The reduction of endothelium glycocalyx degradation may be involved in the underlying mechanism.

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