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Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study
Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permea...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938648/ https://www.ncbi.nlm.nih.gov/pubmed/24587228 http://dx.doi.org/10.1371/journal.pone.0090107 |
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author | Wu, Sheng-Kai Yang, Ming-Tao Kang, Kai-Hsiang Liou, Houng-Chi Lu, Dai-Hua Fu, Wen-Mei Lin, Win-Li |
author_facet | Wu, Sheng-Kai Yang, Ming-Tao Kang, Kai-Hsiang Liou, Houng-Chi Lu, Dai-Hua Fu, Wen-Mei Lin, Win-Li |
author_sort | Wu, Sheng-Kai |
collection | PubMed |
description | Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permeability. In this study, we investigated the effects of MBs/FUS on extending the therapeutic time window of EPO and its neuroprotective effects in both acute and chronic phases. Male Wistar rats were firstly subjected to two common carotid arteries and right middle cerebral artery occlusion (three vessels occlusion, 3VO) for 50 min, and then the rats were treated with hEPO (human recombinant EPO, 5000 IU/kg) with or without MBs/FUS at 5 h after occlusion/reperfusion. Acute phase investigation (I/R, I/R+MBs/FUS, I/R+hEPO, and I/R+hEPO+MBs/FUS) was performed 24 h after I/R; chronic tests including cylinder test and gait analysis were performed one month after I/R. The experimental results showed that MBs/FUS significantly increased the cerebral content of EPO by bettering vascular permeability. In acute phase, both significant improvement of neurological score and reduction of infarct volume were found in the I/R+hEPO+MBs/FUS group, as compared with I/R and I/R+hEPO groups. In chronic phase, long-term behavioral recovery and neuronal loss in brain cortex after I/R injury was significantly improved in the I/R+hEPO+MBs/FUS group. This study indicates that hEPO administration with MBs/FUS sonication even at 5 h after occlusion/reperfusion can produce a significant neuroprotection. |
format | Online Article Text |
id | pubmed-3938648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39386482014-03-04 Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study Wu, Sheng-Kai Yang, Ming-Tao Kang, Kai-Hsiang Liou, Houng-Chi Lu, Dai-Hua Fu, Wen-Mei Lin, Win-Li PLoS One Research Article Erythropoietin (EPO) is a neuroprotective agent against cerebral ischemia/reperfusion (I/R)-induced brain injury. However, its crossing of blood-brain barrier is limited. Focused ultrasound (FUS) sonication with microbubbles (MBs) can effectively open blood-brain barrier to boost the vascular permeability. In this study, we investigated the effects of MBs/FUS on extending the therapeutic time window of EPO and its neuroprotective effects in both acute and chronic phases. Male Wistar rats were firstly subjected to two common carotid arteries and right middle cerebral artery occlusion (three vessels occlusion, 3VO) for 50 min, and then the rats were treated with hEPO (human recombinant EPO, 5000 IU/kg) with or without MBs/FUS at 5 h after occlusion/reperfusion. Acute phase investigation (I/R, I/R+MBs/FUS, I/R+hEPO, and I/R+hEPO+MBs/FUS) was performed 24 h after I/R; chronic tests including cylinder test and gait analysis were performed one month after I/R. The experimental results showed that MBs/FUS significantly increased the cerebral content of EPO by bettering vascular permeability. In acute phase, both significant improvement of neurological score and reduction of infarct volume were found in the I/R+hEPO+MBs/FUS group, as compared with I/R and I/R+hEPO groups. In chronic phase, long-term behavioral recovery and neuronal loss in brain cortex after I/R injury was significantly improved in the I/R+hEPO+MBs/FUS group. This study indicates that hEPO administration with MBs/FUS sonication even at 5 h after occlusion/reperfusion can produce a significant neuroprotection. Public Library of Science 2014-02-28 /pmc/articles/PMC3938648/ /pubmed/24587228 http://dx.doi.org/10.1371/journal.pone.0090107 Text en © 2014 Wu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Wu, Sheng-Kai Yang, Ming-Tao Kang, Kai-Hsiang Liou, Houng-Chi Lu, Dai-Hua Fu, Wen-Mei Lin, Win-Li Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title | Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title_full | Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title_fullStr | Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title_full_unstemmed | Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title_short | Targeted Delivery of Erythropoietin by Transcranial Focused Ultrasound for Neuroprotection against Ischemia/Reperfusion-Induced Neuronal Injury: A Long-Term and Short-Term Study |
title_sort | targeted delivery of erythropoietin by transcranial focused ultrasound for neuroprotection against ischemia/reperfusion-induced neuronal injury: a long-term and short-term study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938648/ https://www.ncbi.nlm.nih.gov/pubmed/24587228 http://dx.doi.org/10.1371/journal.pone.0090107 |
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