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Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes

BACKGROUND: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether i...

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Autores principales: Saxena, Sarah, Nuyens, Vincent, Rodts, Christopher, Jamar, Kristina, Albert, Adelin, Seidel, Laurence, Cherkaoui-Malki, Mustapha, Boogaerts, Jean G., Wulff, Heike, Maze, Mervyn, Kruys, Véronique, Vamecq, Joseph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018926/
https://www.ncbi.nlm.nih.gov/pubmed/36927341
http://dx.doi.org/10.1186/s12871-023-02030-2
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author Saxena, Sarah
Nuyens, Vincent
Rodts, Christopher
Jamar, Kristina
Albert, Adelin
Seidel, Laurence
Cherkaoui-Malki, Mustapha
Boogaerts, Jean G.
Wulff, Heike
Maze, Mervyn
Kruys, Véronique
Vamecq, Joseph
author_facet Saxena, Sarah
Nuyens, Vincent
Rodts, Christopher
Jamar, Kristina
Albert, Adelin
Seidel, Laurence
Cherkaoui-Malki, Mustapha
Boogaerts, Jean G.
Wulff, Heike
Maze, Mervyn
Kruys, Véronique
Vamecq, Joseph
author_sort Saxena, Sarah
collection PubMed
description BACKGROUND: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND. METHODS: Mice (wild-type [WT] and KCa3.1(−/−)) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining. RESULTS: In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1(−/−) mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001). CONCLUSION: Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12871-023-02030-2.
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spelling pubmed-100189262023-03-17 Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes Saxena, Sarah Nuyens, Vincent Rodts, Christopher Jamar, Kristina Albert, Adelin Seidel, Laurence Cherkaoui-Malki, Mustapha Boogaerts, Jean G. Wulff, Heike Maze, Mervyn Kruys, Véronique Vamecq, Joseph BMC Anesthesiol Research BACKGROUND: Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND. METHODS: Mice (wild-type [WT] and KCa3.1(−/−)) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining. RESULTS: In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1(−/−) mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001). CONCLUSION: Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12871-023-02030-2. BioMed Central 2023-03-16 /pmc/articles/PMC10018926/ /pubmed/36927341 http://dx.doi.org/10.1186/s12871-023-02030-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Saxena, Sarah
Nuyens, Vincent
Rodts, Christopher
Jamar, Kristina
Albert, Adelin
Seidel, Laurence
Cherkaoui-Malki, Mustapha
Boogaerts, Jean G.
Wulff, Heike
Maze, Mervyn
Kruys, Véronique
Vamecq, Joseph
Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title_full Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title_fullStr Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title_full_unstemmed Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title_short Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
title_sort involvement of kca3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10018926/
https://www.ncbi.nlm.nih.gov/pubmed/36927341
http://dx.doi.org/10.1186/s12871-023-02030-2
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