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Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats

The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the...

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Autores principales: Zheng, Bin, Zhang, Shuncai, Ying, Yanlu, Guo, Xinying, Li, Hengchang, Xu, Lixin, Ruan, Xiangcai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435454/
https://www.ncbi.nlm.nih.gov/pubmed/30232232
http://dx.doi.org/10.1042/BSR20180892
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author Zheng, Bin
Zhang, Shuncai
Ying, Yanlu
Guo, Xinying
Li, Hengchang
Xu, Lixin
Ruan, Xiangcai
author_facet Zheng, Bin
Zhang, Shuncai
Ying, Yanlu
Guo, Xinying
Li, Hengchang
Xu, Lixin
Ruan, Xiangcai
author_sort Zheng, Bin
collection PubMed
description The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the activation of NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3 inflammasome activity in hippocampus. Rats were subjected to controlled cortical impact method to induce TBI, and treated with Dex. The effect of Dex treatment on the cognitive function, NLRP3 activity, and microglial activation in rat brain tissues was assessed. The administration of Dex improved performance of TBI rats in Morris water maze (MWM) test, which was associated with the increased neurone viability and suppressed microglia activity. Moreover, the administration of Dex inhibited the neuroinflammation in brain tissue as well as the expressions of NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI. The findings outlined in the current study indicated that the improvement effect of Dex on TBI was related to its effect on NLRP3 activity.
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spelling pubmed-64354542019-04-12 Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats Zheng, Bin Zhang, Shuncai Ying, Yanlu Guo, Xinying Li, Hengchang Xu, Lixin Ruan, Xiangcai Biosci Rep Research Articles The abnormally high nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity is a typical characteristic of traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective α-2 adrenergic receptor agonist that inhibits the activation of NLRP3. Thus, it was hypothesized that Dex could attenuate TBI by inhibiting NLRP3 inflammasome activity in hippocampus. Rats were subjected to controlled cortical impact method to induce TBI, and treated with Dex. The effect of Dex treatment on the cognitive function, NLRP3 activity, and microglial activation in rat brain tissues was assessed. The administration of Dex improved performance of TBI rats in Morris water maze (MWM) test, which was associated with the increased neurone viability and suppressed microglia activity. Moreover, the administration of Dex inhibited the neuroinflammation in brain tissue as well as the expressions of NLRP3 and caspase-1. Additionally, Dex and NLRP3 inhibitor, BAY-11-7082 had a synergistic effect in inhibiting NLRP3/caspase-1 axis activity and improving TBI. The findings outlined in the current study indicated that the improvement effect of Dex on TBI was related to its effect on NLRP3 activity. Portland Press Ltd. 2018-10-15 /pmc/articles/PMC6435454/ /pubmed/30232232 http://dx.doi.org/10.1042/BSR20180892 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Zheng, Bin
Zhang, Shuncai
Ying, Yanlu
Guo, Xinying
Li, Hengchang
Xu, Lixin
Ruan, Xiangcai
Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title_full Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title_fullStr Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title_full_unstemmed Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title_short Administration of Dexmedetomidine inhibited NLRP3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
title_sort administration of dexmedetomidine inhibited nlrp3 inflammasome and microglial cell activities in hippocampus of traumatic brain injury rats
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435454/
https://www.ncbi.nlm.nih.gov/pubmed/30232232
http://dx.doi.org/10.1042/BSR20180892
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