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Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits

BACKGROUND: Dexmedetomidine (Dex) can improve neuronal viability and protect the spinal cord from ischemia–reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study investigated the effects of dexmedetomidine on the toll-like receptor 4 (TLR4)-mediated nuclear fact...

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Autores principales: Sun, Zhixiang, Zhao, Tianyun, Lv, Shaojun, Gao, Ying, Masters, Joe, Weng, Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054716/
https://www.ncbi.nlm.nih.gov/pubmed/30031397
http://dx.doi.org/10.1186/s12967-018-1583-7
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author Sun, Zhixiang
Zhao, Tianyun
Lv, Shaojun
Gao, Ying
Masters, Joe
Weng, Hao
author_facet Sun, Zhixiang
Zhao, Tianyun
Lv, Shaojun
Gao, Ying
Masters, Joe
Weng, Hao
author_sort Sun, Zhixiang
collection PubMed
description BACKGROUND: Dexmedetomidine (Dex) can improve neuronal viability and protect the spinal cord from ischemia–reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study investigated the effects of dexmedetomidine on the toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NF-κB) inflammatory system and caspase-3 dependent apoptosis induced by spinal cord ischemia–reperfusion injury. METHODS: Twenty-four rabbits were divided into three groups: I/R, Dex (10 µg/kg/h prior to ischemia until reperfusion), and Sham. Abdominal aortic occlusion was carried out for 30 min in the I/R and Dex groups. Hindlimb motor function was assessed using the Tarlov scoring system for gait evaluation. Motor neuron survival and apoptosis in the ventral grey matter were assessed by haematoxylin–eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling staining. The expression and localisation of ionised calcium-binding adaptor molecule 1, TLR4, NF-κB and caspase-3 were assessed by immunoreactivity analysis. The levels of interleukin 1β and tumour necrosis factor α were assessed using enzyme-linked immunosorbent assays. RESULTS: Perioperative treatment with dexmedetomidine was associated with a significant preservation of locomotor function following spinal cord ischemia–reperfusion injury with increased neuronal survival in the spinal cord compared to control. In addition, dexmedetomidine suppressed microglial activation, inhibited the TLR4-mediated NF-κB signalling pathway, and inhibited the caspase-3 dependent apoptosis. CONCLUSIONS: Dexmedetomidine confers neuroprotection against spinal cord ischemia–reperfusion injury through suppression of spinal cord inflammation and neuronal apoptosis. A reduction in microglial activation and inhibition of both the TLR4-mediated NF-κB signalling pathway and caspase-3 dependent apoptosis are implicated.
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spelling pubmed-60547162018-07-23 Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits Sun, Zhixiang Zhao, Tianyun Lv, Shaojun Gao, Ying Masters, Joe Weng, Hao J Transl Med Research BACKGROUND: Dexmedetomidine (Dex) can improve neuronal viability and protect the spinal cord from ischemia–reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. This study investigated the effects of dexmedetomidine on the toll-like receptor 4 (TLR4)-mediated nuclear factor κB (NF-κB) inflammatory system and caspase-3 dependent apoptosis induced by spinal cord ischemia–reperfusion injury. METHODS: Twenty-four rabbits were divided into three groups: I/R, Dex (10 µg/kg/h prior to ischemia until reperfusion), and Sham. Abdominal aortic occlusion was carried out for 30 min in the I/R and Dex groups. Hindlimb motor function was assessed using the Tarlov scoring system for gait evaluation. Motor neuron survival and apoptosis in the ventral grey matter were assessed by haematoxylin–eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labelling staining. The expression and localisation of ionised calcium-binding adaptor molecule 1, TLR4, NF-κB and caspase-3 were assessed by immunoreactivity analysis. The levels of interleukin 1β and tumour necrosis factor α were assessed using enzyme-linked immunosorbent assays. RESULTS: Perioperative treatment with dexmedetomidine was associated with a significant preservation of locomotor function following spinal cord ischemia–reperfusion injury with increased neuronal survival in the spinal cord compared to control. In addition, dexmedetomidine suppressed microglial activation, inhibited the TLR4-mediated NF-κB signalling pathway, and inhibited the caspase-3 dependent apoptosis. CONCLUSIONS: Dexmedetomidine confers neuroprotection against spinal cord ischemia–reperfusion injury through suppression of spinal cord inflammation and neuronal apoptosis. A reduction in microglial activation and inhibition of both the TLR4-mediated NF-κB signalling pathway and caspase-3 dependent apoptosis are implicated. BioMed Central 2018-07-21 /pmc/articles/PMC6054716/ /pubmed/30031397 http://dx.doi.org/10.1186/s12967-018-1583-7 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sun, Zhixiang
Zhao, Tianyun
Lv, Shaojun
Gao, Ying
Masters, Joe
Weng, Hao
Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title_full Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title_fullStr Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title_full_unstemmed Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title_short Dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
title_sort dexmedetomidine attenuates spinal cord ischemia–reperfusion injury through both anti-inflammation and anti-apoptosis mechanisms in rabbits
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054716/
https://www.ncbi.nlm.nih.gov/pubmed/30031397
http://dx.doi.org/10.1186/s12967-018-1583-7
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