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

被引:61
作者
Li, Fang [1 ]
Zhao, Liang [1 ]
Shi, Yijie [1 ]
Liang, Jia [2 ]
机构
[1] Jinzhou Med Univ, Sch Pharm, Jinzhou 121000, Peoples R China
[2] Jinzhou Med Univ, Life Sci Inst, Jinzhou 121000, Peoples R China
基金
中国国家自然科学基金;
关键词
stroke; edaravone; macrophage; exosomes; TISSUE-PLASMINOGEN ACTIVATOR; EXTRACELLULAR VESICLES; ISCHEMIC-STROKE; BRAIN-INJURY; DELIVERY; NEUROGENESIS; RECOVERY; MCI-186;
D O I
10.1021/acs.molpharmaceut.0c00245
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:3192 / 3201
页数:10
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