Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yang, Fu, Naisheng, Su, Jiangli, Wang, Xiumei, Li, Xiaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425296/
https://www.ncbi.nlm.nih.gov/pubmed/30949500
http://dx.doi.org/10.1155/2019/4273290
_version_ 1783404814127857664
author Liu, Yang
Fu, Naisheng
Su, Jiangli
Wang, Xiumei
Li, Xiaohua
author_facet Liu, Yang
Fu, Naisheng
Su, Jiangli
Wang, Xiumei
Li, Xiaohua
author_sort Liu, Yang
collection PubMed
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.
format Online
Article
Text
id pubmed-6425296
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-64252962019-04-04 Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3 Liu, Yang Fu, Naisheng Su, Jiangli Wang, Xiumei Li, Xiaohua Biomed Res Int Research Article 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. Hindawi 2019-03-04 /pmc/articles/PMC6425296/ /pubmed/30949500 http://dx.doi.org/10.1155/2019/4273290 Text en Copyright © 2019 Yang Liu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Yang
Fu, Naisheng
Su, Jiangli
Wang, Xiumei
Li, Xiaohua
Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title_full Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title_fullStr Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title_full_unstemmed Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title_short Rapid Enkephalin Delivery Using Exosomes to Promote Neurons Recovery in Ischemic Stroke by Inhibiting Neuronal p53/Caspase-3
title_sort rapid enkephalin delivery using exosomes to promote neurons recovery in ischemic stroke by inhibiting neuronal p53/caspase-3
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425296/
https://www.ncbi.nlm.nih.gov/pubmed/30949500
http://dx.doi.org/10.1155/2019/4273290
work_keys_str_mv AT liuyang rapidenkephalindeliveryusingexosomestopromoteneuronsrecoveryinischemicstrokebyinhibitingneuronalp53caspase3
AT funaisheng rapidenkephalindeliveryusingexosomestopromoteneuronsrecoveryinischemicstrokebyinhibitingneuronalp53caspase3
AT sujiangli rapidenkephalindeliveryusingexosomestopromoteneuronsrecoveryinischemicstrokebyinhibitingneuronalp53caspase3
AT wangxiumei rapidenkephalindeliveryusingexosomestopromoteneuronsrecoveryinischemicstrokebyinhibitingneuronalp53caspase3
AT lixiaohua rapidenkephalindeliveryusingexosomestopromoteneuronsrecoveryinischemicstrokebyinhibitingneuronalp53caspase3