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Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of...

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Autores principales: Guo, Hao, Zhang, Weiwei, Wang, Zhi, Li, Zhishan, Zhou, Jing, Yang, Zhaoyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512049/
https://www.ncbi.nlm.nih.gov/pubmed/36172260
http://dx.doi.org/10.3389/fnmol.2022.977941
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author Guo, Hao
Zhang, Weiwei
Wang, Zhi
Li, Zhishan
Zhou, Jing
Yang, Zhaoyu
author_facet Guo, Hao
Zhang, Weiwei
Wang, Zhi
Li, Zhishan
Zhou, Jing
Yang, Zhaoyu
author_sort Guo, Hao
collection PubMed
description Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of ICH was established. The rats were randomly divided into the sham group, the ICH group, and the ICH + DEX group. Neurological outcomes, neuronal injury, and apoptosis were evaluated. Brain water content, Evans blue extravasation, and the expression of tight junction-associated proteins were also detected to assess the blood-brain barrier (BBB) integrity. Subsequently, the microglia/macrophage polarization state and inflammatory cytokine levels were observed. To further explore the underlying mechanism, NF-κB signaling pathway-associated proteins were detected. The results showed that DEX exerted neuroprotective effects against ICH-induced neurological deficits. DEX significantly increased the numbers of the surviving neurons and ameliorated neuronal cell loss and apoptosis in ICH. The rats that received the DEX displayed a lower level of brain water content and EB extravasation, moreover, ZO-1, occludin, and claudin-5 were markedly increased by DEX. Additionally, DEX facilitated M2 microglia/macrophage polarization, the M1-associated markers were reduced by DEX, while the M2-associated identification significantly increased. We found that DEX dramatically diminished pro-inflammatory cytokines expression, simultaneously promoting anti-inflammatory cytokines expression. DEX inhibited nuclear translocation of NF-κB in ICH rats. Our data suggest that DEX post-conditioning protects BBB integrity by modulating microglia/macrophage polarization via inhibiting the NF-κB signaling pathway in ICH.
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spelling pubmed-95120492022-09-27 Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage Guo, Hao Zhang, Weiwei Wang, Zhi Li, Zhishan Zhou, Jing Yang, Zhaoyu Front Mol Neurosci Neuroscience Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of ICH was established. The rats were randomly divided into the sham group, the ICH group, and the ICH + DEX group. Neurological outcomes, neuronal injury, and apoptosis were evaluated. Brain water content, Evans blue extravasation, and the expression of tight junction-associated proteins were also detected to assess the blood-brain barrier (BBB) integrity. Subsequently, the microglia/macrophage polarization state and inflammatory cytokine levels were observed. To further explore the underlying mechanism, NF-κB signaling pathway-associated proteins were detected. The results showed that DEX exerted neuroprotective effects against ICH-induced neurological deficits. DEX significantly increased the numbers of the surviving neurons and ameliorated neuronal cell loss and apoptosis in ICH. The rats that received the DEX displayed a lower level of brain water content and EB extravasation, moreover, ZO-1, occludin, and claudin-5 were markedly increased by DEX. Additionally, DEX facilitated M2 microglia/macrophage polarization, the M1-associated markers were reduced by DEX, while the M2-associated identification significantly increased. We found that DEX dramatically diminished pro-inflammatory cytokines expression, simultaneously promoting anti-inflammatory cytokines expression. DEX inhibited nuclear translocation of NF-κB in ICH rats. Our data suggest that DEX post-conditioning protects BBB integrity by modulating microglia/macrophage polarization via inhibiting the NF-κB signaling pathway in ICH. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9512049/ /pubmed/36172260 http://dx.doi.org/10.3389/fnmol.2022.977941 Text en Copyright © 2022 Guo, Zhang, Wang, Li, Zhou and Yang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Guo, Hao
Zhang, Weiwei
Wang, Zhi
Li, Zhishan
Zhou, Jing
Yang, Zhaoyu
Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title_full Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title_fullStr Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title_full_unstemmed Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title_short Dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting NF-κB signaling pathway in intracerebral hemorrhage
title_sort dexmedetomidine post-conditioning protects blood-brain barrier integrity by modulating microglia/macrophage polarization via inhibiting nf-κb signaling pathway in intracerebral hemorrhage
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512049/
https://www.ncbi.nlm.nih.gov/pubmed/36172260
http://dx.doi.org/10.3389/fnmol.2022.977941
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