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

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. Immun...

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Veröffentlicht in:BioMed research international 2019-01, Vol.2019 (2019), p.1-11
Hauptverfasser: Wang, Xiumei, Su, Jiangli, Fu, Naisheng, Liu, Yang, Li, Xiaohua
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Su, Jiangli
Fu, Naisheng
Liu, Yang
Li, Xiaohua
description 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 vitro studies 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. An in vivo experiment 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.
doi_str_mv 10.1155/2019/4273290
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subjects Animal experimentation
Apoptosis
Blood-brain barrier
Brain
Brain damage
Brain injury
Brain research
Caspase
Caspase-3
Cell culture
Cerebral blood flow
Drug therapy
Enkephalins
Exosomes
Gene expression
Glutamate
Hippocampus
Immunofluorescence
Ischemia
Metabolism
Narcotics
Neurons
Neurosciences
Occlusion
p53 Protein
Pharmacology
Recovery
Regeneration
Reperfusion
Stem cells
Stroke
Stroke (Disease)
Tar
Transferrin
Transferrins
Tumor proteins
title Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
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