Edaravone-Loaded Macrophage-Derived Exosomes Enhance Neuroprotection in the Rat Permanent Middle Cerebral Artery Occlusion Model of Stroke.,Molecular Pharmaceutics

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Edaravone-Loaded Macrophage-Derived Exosomes Enhance Neuroprotection in the Rat Permanent Middle Cerebral Artery Occlusion Model of Stroke.
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2020-07-30 , DOI: 10.1021/acs.molpharmaceut.0c00245
Fang Li ₁ , Liang Zhao ₁ , Yijie Shi ₁ , Jia Liang ₂

Affiliation

Edaravone (Edv) can inhibit tissue damage, cause cerebral edema, and delay neuronal death caused by acute cerebral infarction. Exosomes are considered as cargo carriers for intercellular communication and serve as important regulators in many pathological processes. Here, we developed macrophage-derived exosomes (Exo) containing Edv (Exo + Edv) to improve the bioavailability of Edv and enhance the neuroprotective effects in a rat model of permanent middle cerebral artery occlusion (PMCAO). The results showed that Exo + Edv significantly improved the bioavailability of Edv and prolonged half-life (t_1/2). At the same time, Exo + Edv made Edv more easily reach the ischemic side of rats with PMCAO and was localized with neuronal cells and microglia, thus reducing the death of neuronal cells and promoting the polarization of microglia from M1 to M2. Taken together, Exo + Edv may become a potential clinical treatment option for PMCAO.

中文翻译：

依达拉奉负载巨噬细胞衍生的外来体增强中风大鼠永久性中脑动脉闭塞模型中的神经保护。

依达拉奉（Edv）可以抑制组织损伤，引起脑水肿并延迟由急性脑梗死引起的神经元死亡。外泌体被认为是细胞间通讯的货物载体，并在许多病理过程中起重要的调节作用。在这里，我们开发了含有Edv（Exo + Edv）的巨噬细胞来源的外来体（Exo），以改善Edv的生物利用度并增强永久性大脑中动脉阻塞（PMCAO）大鼠模型的神经保护作用。结果表明，Exo + Edv显着提高了Edv的生物利用度并延长了半衰期（t _1/2）。同时，Exo + Edv使PMVAO更容易使Edv到达大鼠的缺血侧，并定位于神经元细胞和小胶质细胞，从而减少了神经元细胞的死亡并促进了小胶质细胞从M1到M2的极化。两者合计，Exo + Edv可能成为PMCAO的潜在临床治疗选择。

更新日期：2020-09-09

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