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 |
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Rok vydání: | 2019 |
Předmět: |
Male
Article Subject Enkephalin lcsh:Medicine Caspase 3 Hippocampal formation Pharmacology Blood–brain barrier General Biochemistry Genetics and Molecular Biology Brain Ischemia medicine Animals Stroke Neurons chemistry.chemical_classification General Immunology and Microbiology Chemistry lcsh:R digestive oral and skin physiology Glutamate receptor Enkephalins General Medicine medicine.disease Rats Neuroprotective Agents medicine.anatomical_structure nervous system Transferrin Neuron Tumor Suppressor Protein p53 Research Article |
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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