Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3

Autor: Jiangli Su, Liu Yang, Li Xiaohua, Xiumei Wang, Fu Naisheng
Rok vydání: 2019
Předmět:
Zdroj: BioMed Research International
BioMed Research International, Vol 2019 (2019)
ISSN: 2314-6141
2314-6133
DOI: 10.1155/2019/4273290
Popis: No pharmacological treatment is currently available to protect brain from neuronal damage after ischemic stroke. Recent studies found that enkephalin may play an important role in neuron regeneration. We assembled a homogeneous size vesicle constituted by transferrin, exosomes, and enkephalin. Immunofluorescence assay showed that transferrin was combined with the exosomes and enkephalin was packaged into the vesicle; thus this complex was called tar-exo-enkephalin.In vitrostudies were performed using rat primary hippocampal neurons and the results showed that enkephalin decreased p53 and caspase-3 levels to 47.6% and 67.2%, respectively, compared to neurons treated with glutamate, thus inhibiting neuron apoptosis caused by glutamate. Anin vivoexperiment in rats was also carried out using a transient middle cerebral artery occlusion (tMCAO)/reperfusion model and tar-exo-enkephalin treatment was performed after tMCAO. The results showed that tar-exo-enkephalin crossed the blood brain barrier (BBB) and decreased the levels of LDH, p53, caspase-3, and NO by 41.9, 52.6, 45.5, and 57.9% compared to the tMCAO rats, respectively. In addition, tar-exo-enkephalin improved brain neuron density and neurological score after tMCAO. These findings suggest that the use of exogenous enkephalin might promote neurological recovery after stroke.
Databáze: OpenAIRE
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