Edaravone-Loaded Macrophage-Derived Exosomes Enhance Neuroprotection in the Rat Permanent Middle Cerebral Artery Occlusion Model of Stroke.
Fang LiLiang ZhaoYijie ShiJia LiangPublished in: Molecular pharmaceutics (2020)
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 (t1/2). 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.
Keyphrases
- middle cerebral artery
- cerebral ischemia
- induced apoptosis
- mesenchymal stem cells
- internal carotid artery
- stem cells
- cell cycle arrest
- subarachnoid hemorrhage
- oxidative stress
- adipose tissue
- inflammatory response
- brain injury
- endoplasmic reticulum stress
- blood brain barrier
- drug delivery
- atrial fibrillation
- liver failure
- neuropathic pain
- pi k akt
- intensive care unit
- climate change
- acute respiratory distress syndrome
- wound healing
- cerebral blood flow