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APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats
APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JKL International LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988600/ https://www.ncbi.nlm.nih.gov/pubmed/29896433 http://dx.doi.org/10.14336/AD.2017.1130 |
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author | Yan, Tao Venkat, Poornima Chopp, Michael Zacharek, Alex Yu, Peng Ning, Ruizhuo Qiao, Xiaoxi Kelley, Mark R. Chen, Jieli |
author_facet | Yan, Tao Venkat, Poornima Chopp, Michael Zacharek, Alex Yu, Peng Ning, Ruizhuo Qiao, Xiaoxi Kelley, Mark R. Chen, Jieli |
author_sort | Yan, Tao |
collection | PubMed |
description | APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebral artery occlusion (MCAo) and treated with either PBS or APX3330 (10mg/kg, oral gavage) starting at 24h after MCAo, and daily for 14 days. Rats were sacrificed at 14 days after MCAo and, blood brain barrier (BBB) permeability, ischemic lesion volume, immunohistochemistry, cell death assay, Western blot, real time PCR, and angiogenic ELISA array were performed. Compared to PBS treatment, APX3330 treatment of stroke in T1DM rats significantly improves neurological functional outcome, decreases lesion volume, and improves BBB integrity as well as decreases total vessel density and VEGF expression, while significantly increases arterial density in the ischemic border zone (IBZ). APX3330 significantly increases myelin density, oligodendrocyte number, oligodendrocyte progenitor cell number, synaptic protein expression, and induces M2 macrophage polarization in the IBZ of T1DM stroke rats. Compared to PBS treatment, APX3330 treatment significantly decreases plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 and matrix metalloproteinase 9 (MMP9) and receptor for advanced glycation endproducts expression in the ischemic brain of T1DM stroke rats. APX3330 treatment significantly decreases cell death and MMP9 and PAI-1 gene expression in cultured primary cortical neurons subjected to high glucose and oxygen glucose deprivation, compared to untreated control cells. APX3330 treatment increases M2 macrophage polarization and decreases inflammatory factor expression in the ischemic brain as well as promotes neuroprotective and neurorestorative effects after stroke in T1DM rats. |
format | Online Article Text |
id | pubmed-5988600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59886002018-06-12 APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats Yan, Tao Venkat, Poornima Chopp, Michael Zacharek, Alex Yu, Peng Ning, Ruizhuo Qiao, Xiaoxi Kelley, Mark R. Chen, Jieli Aging Dis Orginal Article APX3330 is a selective inhibitor of APE1/Ref-1 redox activity. In this study, we investigate the therapeutic effects and underlying mechanisms of APX3330 treatment in type one diabetes mellitus (T1DM) stroke rats. Adult male Wistar rats were induced with T1DM and subjected to transient middle cerebral artery occlusion (MCAo) and treated with either PBS or APX3330 (10mg/kg, oral gavage) starting at 24h after MCAo, and daily for 14 days. Rats were sacrificed at 14 days after MCAo and, blood brain barrier (BBB) permeability, ischemic lesion volume, immunohistochemistry, cell death assay, Western blot, real time PCR, and angiogenic ELISA array were performed. Compared to PBS treatment, APX3330 treatment of stroke in T1DM rats significantly improves neurological functional outcome, decreases lesion volume, and improves BBB integrity as well as decreases total vessel density and VEGF expression, while significantly increases arterial density in the ischemic border zone (IBZ). APX3330 significantly increases myelin density, oligodendrocyte number, oligodendrocyte progenitor cell number, synaptic protein expression, and induces M2 macrophage polarization in the IBZ of T1DM stroke rats. Compared to PBS treatment, APX3330 treatment significantly decreases plasminogen activator inhibitor type-1 (PAI-1), monocyte chemotactic protein-1 and matrix metalloproteinase 9 (MMP9) and receptor for advanced glycation endproducts expression in the ischemic brain of T1DM stroke rats. APX3330 treatment significantly decreases cell death and MMP9 and PAI-1 gene expression in cultured primary cortical neurons subjected to high glucose and oxygen glucose deprivation, compared to untreated control cells. APX3330 treatment increases M2 macrophage polarization and decreases inflammatory factor expression in the ischemic brain as well as promotes neuroprotective and neurorestorative effects after stroke in T1DM rats. JKL International LLC 2018-06-01 /pmc/articles/PMC5988600/ /pubmed/29896433 http://dx.doi.org/10.14336/AD.2017.1130 Text en Copyright: © 2018 Yan et al. http://creativecommons.org/licenses/by/2.0/ 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 that the original work is properly attributed. |
spellingShingle | Orginal Article Yan, Tao Venkat, Poornima Chopp, Michael Zacharek, Alex Yu, Peng Ning, Ruizhuo Qiao, Xiaoxi Kelley, Mark R. Chen, Jieli APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title | APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title_full | APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title_fullStr | APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title_full_unstemmed | APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title_short | APX3330 Promotes Neurorestorative Effects after Stroke in Type One Diabetic Rats |
title_sort | apx3330 promotes neurorestorative effects after stroke in type one diabetic rats |
topic | Orginal Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988600/ https://www.ncbi.nlm.nih.gov/pubmed/29896433 http://dx.doi.org/10.14336/AD.2017.1130 |
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