Ischemic stroke (IS) is a leading cause of morbidity and mortality globally. This study aimed to investigate the role of exosomes (Exo) derived from bone marrow mesenchymal stem cells (BMSCs) treated with Musk Ketone (Mus treated-Exo) in the development of IS injury. BMSCs were pretreated with 10 μM Mus for 36 hours, and Exo derived from these Mus-treated BMSCs (Mus-treated Exo) were extracted. Rats with middle cerebral artery occlusion (MCAO) were administered either 2 mg/kg of control Exo (Ctrl-Exo), 2 mg/kg of Mus treated-Exo, or 10 μM Mus. Neurological deficit and cerebral infarction in the MCAO rats were assessed utilizing neurological scores and TTC staining. Neuronal apoptosis, activation of microglia/macrophages, and inflammation were evaluated through TUNEL staining, immunofluorescence staining, and western blot analysis, respectively. Our findings revealed that Mus-treated Exo possessed a more pronounced neuroprotective effect on MCAO rats when compared to Ctrl-Exo and Mus treatment alone. Specifically, Mus treated-Exo effectively ameliorated neurological function, reduced the volume of cerebral infarction, and diminished hemispheric swelling in MCAO rats. Moreover, it inhibited neuronal apoptosis and activation of microglia/macrophages, promoted the expression of the anti-apoptotic protein Bcl-2 while decreasing the expression of pro-apoptotic protein Bax, Cleaved-caspase 3, and pro-inflammatory factors IL-6 and COX-2. The findings imply that Mus treated-Exo could confer neuroprotection in rats affected by IS, potentially by attenuating apoptosis and neuroinflammation. The underlying mechanisms, however, warrant further investigation. Mus treated-Exo shows potential as a new therapeutic strategy for IS.

中文翻译：

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麝香酮处理的骨髓间充质干细胞来源的外泌体对缺血性脑卒中大鼠的神经保护作用

缺血性中风（IS）是全球发病率和死亡率的主要原因。本研究旨在探讨经麝香酮（Mus treat-Exo）处理的骨髓间充质干细胞（BMSCs）衍生的外泌体（Exo）在IS损伤发展中的作用。将BMSC用10μM Mus预处理36小时，提取源自这些Mus处理的BMSC的Exo（Mus处理的Exo）。大脑中动脉闭塞（MCAO）的大鼠被给予2mg/kg的对照Exo（Ctrl-Exo）、2mg/kg的Mus处理的Exo或10μM Mus。利用神经评分和 TTC 染色评估 MCAO 大鼠的神经功能缺损和脑梗塞。分别通过TUNEL染色、免疫荧光染色和蛋白质印迹分析评估神经元凋亡、小胶质细胞/巨噬细胞的活化和炎症。我们的研究结果表明，与单独的 Ctrl-Exo 和 Mus 治疗相比，Mus 治疗的 Exo 对 MCAO 大鼠具有更明显的神经保护作用。具体来说，Mus-Exo 治疗可有效改善 MCAO 大鼠的神经功能、减少脑梗塞体积并减少半球肿胀。此外，它还抑制神经元凋亡和小胶质细胞/巨噬细胞的活化，促进抗凋亡蛋白 Bcl-2 的表达，同时降低促凋亡蛋白 Bax、Cleaved-caspase 3 和促炎因子 IL-6 和环氧化酶-2。研究结果表明，Mus 处理的 Exo 可以通过减轻细胞凋亡和神经炎症，为受 IS 影响的大鼠提供神经保护。然而，其潜在机制值得进一步研究。Mus 处理的 Exo 显示出作为 IS 新治疗策略的潜力。