Effects of stem cell-derived exosomes on neuronal apoptosis and inflammatory cytokines in rats with cerebral ischemia-reperfusion injury via PI3K/AKT pathway-mediated mitochondrial apoptosis

Abstract

Objective This study aimed to investigate the effects of stem cell-derived exosomes (SC-Exos) on learning, memory, and neuronal apoptosis in rats with cerebral ischemia-reperfusion injury and to determine whether SC-Exos exert their effects via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway-mediated mitochondrial pathways of apoptosis. Materials and methods Eighty rats were randomly allocated to control, model, SC-Exos, and PI3K inhibitor groups. A model of focal cerebral ischemia-reperfusion was established using the improved Longa method. Expression of interleukin-1α (IL-1α), interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were compared in the brains and serum of each group. The expressions of Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, cytochrome C (CytC), PI3K, and AKT-related genes and proteins were evaluated by real-time quantitative polymerase chain reaction and western blotting. Results The SC-Exos-group exhibited more novel entries, less latency for the novel arm, and fewer entries into the starting arm and other arms than the model group (p<.05). Lower expression of the inflammatory cytokines IL-1α, IL-2, and TNF-α and higher expression of IFN-γ were observed in the SC-Exos group than in the model group. TdT-mediated dUTP nick end labeling (TUNEL) assay showed that lower neural cell apoptosis rate and expression of Bax, cleaved-caspase-3, cleaved-caspase-9, CytC, PI3K, and AKT mRNA and proteins and higher expression of Bcl-2 mRNA and protein were observed in the SC-Exos group than in the model group (p<.05). Conclusions SC-Exos can significantly ameliorate brain injury caused by cerebral ischemia-reperfusion. The mechanism may be a novel therapeutic target for ischemia-reperfusion injury.